The draw was made in Nyon on Monday afternoon, with the Giallorossi paired with the Ukrainian champions.
The two legs will take place in February and March.
“The draw in Nyon has given us a very difficult opponent for the last-16,” Di Francesco said. “Over the last few months I have followed Shakhtar Donetsk closely: they are a well-organised side from a tactical standpoint, thanks to the work of Paulo Fonseca, who I believe is a great coach.
“They qualified from a tough group – eliminating Napoli, who are one of the best sides in Italy. There are a lot of reasons to respect them as opponents, but there are just as many reasons why we must go out on the pitch and give everything to qualify for the next round.”
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