Can the Giallorossi continue the strong form they have shown in the competition so far - against another opponent with high aspirations for this season?
The Giallorossi enter this tie on the back of successive domestic defeats, against rivals Lazio in the first leg of the Coppa Italia semi-finals (2-0) and, on Sunday, against Napoli in the league at the Stadio Olimpico (2-1).
In the Europa League, however, Roma have been comfortable all season - topping Group E with three wins and three draws before progressing 4-1 on aggregate against Villarreal in the first knockout stage.
Olympique Lyon, meanwhile, sit fourth in Ligue 1, some way adrift of the top three and with a fight on their hands to sustain that position. Their last game saw them draw 1-1 with Bordeaux.
In Europe this season they began in the Champions League, being knocked out of a group that was topped by Juventus with Sevilla in second place.
As a result Bruno Genesio's side dropped into the Europa League, where they opened up the knockout stage with an 11-2 aggregate hammering of Dutch side AZ Alkmaar.
This content is provided by a third party. Because of the choice you have made about cookies on our
website, the external site does not have permission to display here.
If you would like to see the content, please change your cookie choices using either of the buttons
shown.
Roma have almost a full squad to choose from, with Antonio Rudiger (suspended) the one major absentee from the contest.
Elsewhere Alessandro Florenzi remains a long-term injury absentee, while former Lyon player Clement Grenier - who travelled with the squad to his old stomping ground - is ineligible for the competition.
Lyon are similarly free of major worries ahead of the game - although their major January arrival, Memphis Depay, is also ineligible.
Bruno Genesio: “The matches against Juventus showed us that we can cause a big team lots of trouble. I think that this tie will be different but it may also be beneficial to us... We've studied this team a lot and the way in which they attack. Patience is one of the things we'll need to maintain against this type of the team: one that is tactically very well-prepared.
"We need to be capable of wrapping this match up, of having a creative spark while at same time keeping our balance. It'll be important to not concede... I count on Maxime Gonalons, he is our captain and he has everybody's confidence. He'll start tomorrow.”
Luciano Spalletti: “When they met Juventus earlier in the season they played very well in both games. It will be tough because the French league has improved in the last few years. When we played them in 2007, Lyon were the only really good team in the league; now there are sides like PSG, Monaco and Nice – it's more competitive. Back then you could sometimes catch them off guard but now they're used to playing top-level games, both technically and physically.
"They're clearly very talented and we'll need to be careful not to leave any open spaces because they have tremendous pace up front. If you let [Alexandre] Lacazette have space, he can really unleash his ability. You either go into their half and snap at their heels, or you let them have the ball and wait in your half for them. If you try and do half measures you could hand them a huge advantage.”
In some quarters, this has been billed as a clash between two of the most prolific strikers in Europe this season. Edin Dzeko might be the Europa League's top goalscorer right now but, in Alex Lacazette, Lyon have a prime threat of their own.
"He's one of the best forwards in Europe, he has it all," Lacazette said on Wednesday. "I might be quicker but he's much better in the air than me.
"I don't play to prove myself to those who doubt me. I just want to score for my team. I'm not under any particular pressure. I'm as keen as I am in every match but maybe a little keener in these types of matches to show my teammates that they can rely on me."
The France international insists that the Europa League is a major target for both him and his team this season. Fit, in-form and full of determination, Lacazette's combination of pace, power and eye for goal will make him one of the more dangerous attackers the Giallorossi defence faces this season.
"We'll have our chances," he added. "Roma is a very big team. We have to work hard tomorrow. If I have only once chance, it'll be up to me to put it away."
Read more on Lyon's dangermen here.
While all eyes will be on Edin Dzeko as he looks to continue his recent form on the continent, it is in defence where Roma will perhaps have to be particularly diligent. One of the most improved performers this season has been full-back Emerson Palmieri, who will be looking to continue his development on another big stage.
It was the Brazilian who turned the tie against Villarreal in the last round, lashing into the top corner from 25 yards to break the deadlock and lay the groundwork for Dzeko's hat-trick. While a similar impact this time around would be most welcome, his primary task will be to ensure Lyon's wide players cannot get the better of him.
"It will be very difficult," Emerson said this week. "Lyon play very attacking football and we'll need to be careful.
"However, the tie lasts 180 minutes and we need to do well in the first leg in France. We have to play our [own] game."
Read more from Emerson Palmieri here.
This content is provided by a third party. Because of the choice you have made about cookies on our
website, the external site does not have permission to display here.
If you would like to see the content, please change your cookie choices using either of the buttons
shown.
Spalletti faces a few decisions ahead of the game, the boss pondering how much to change things around after two successive defeats in domestic competition.
It seems almost certain that Alisson will continue in goal - as he has done in all the cup competitions - while Rudiger's suspension means a three-man defence of Fazio, Manolas and Jesus appears likely.
Further forward, it remains to be seen whether Leandro Paredes is preferred to Kevin Strootman or Daniele De Rossi, while Diego Perotti's impressive display in the defeat to Napoli could see him given another starting opportunity in support of Dzeko.
Bruno Genesio has a wealth of attacking options to choose from, and it will be interesting to see which ones he chooses to deploy in this match.
The boss has already confirmed that Maxime Gonalons will captain the side, and he could be tasked with offering protection and motivation to a spine of the team that perhaps lacks his experience of this sort of clash.
In attack, however, Genesio could let youthful exuberance ran wild - with the dangerous Lacazette flanked by the young and talented duo of Nabil Fekir and Maxwel Cornet.
This content is provided by a third party. Because of the choice you have made about cookies on our
website, the external site does not have permission to display here.
If you would like to see the content, please change your cookie choices using either of the buttons
shown.
I confirm that I have read the privacy policy.
© 2018-2024 Soccer S.r.l. – EU VAT IT09305501000 - all rights reserved. The AS Roma names, logos and artwork are registered or unregistered trademarks of Soccer S.r.l. All other trademarks may be the property of their respective holders.