Roma are forced to completely transform their team with Bryan Cristante in a three-man defence against Gervinho and Dejan Kulusevski’s Parma.
It kicks off at the Stadio Olimpico at 20.45 UK time (19.45 GMT).
Both these teams are coming off three consecutive defeats, but while the Ducali are comfortably mid-table, the Giallorossi risk losing their place in Europe and Coach Paulo Fonseca’s job.
Adding to the drama, Justin Kluivert is dropped from the squad for a poor attitude in training, with Chris Smalling and Davide Santon injured, also Davide Zappacosta not 100 per cent fit.
With a shortage of options, midfielder Cristante is moved to the centre of a three-man defence.
There are adjustments upfront too, with Lorenzo Pellegrini and Henrikh Mkhitaryan in a double trequartista symbol feeding Edin Dzeko.
Bruno Peres is a surprise pick on the right wing, with off-form Amadou Diawara in midfield.
Parma are also coming off three consecutive defeats against Inter, Verona and Fiorentina.
Andreas Cornelius returns after he was rested at the weekend, in a trio with Kulusevski and ex-Roma star Gervinho.
All the Serie A sides are walking out to the music of Ennio Morricone in this round to mark his passing at the age of 91, but he was a passionate Roma fan, so the Giallorossi will also wear a special patch for the Maestro.
Roma: Pau Lopez; Mancini, Cristante, Ibanez; Bruno Peres, Diawara, Veretout, Spinazzola; Pellegrini, Mkhitaryan; Dzeko
Parma: Sepe; Darmian, Iacoponi, Bruno Alves, Pezzella; Kucka, Hernani, Barillà; Kulusevski, Cornelius, Gervinho
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