Yunus Musah is favourite to start over Ismael Bennacer in centre midfield for Milan, while Lorenzo Pellegrini and Paulo Dybala return to the Giallorossi line-up in the second leg of the Europa League quarter-finals.
It kicks off at 20:00 UK time (GMT+1). Roma beat Milan 1-0 in the first leg at San Siro last week.
The Giallorossi are without the suspended Bryan Cristante, the injured Sardar Azmoun, plus Evan Ndicka (resting), Dean Huijsen and Rasmus Kristensen (out of UEFA list).
Chris Smalling and Gianluca Mancini will return to the starting XI and the same is true of Stephan El Shaarawy, Dybala and Pellegrini who had started on the bench against Udinese.
De Rossi is expected to use a 4-4-2 system again with El Sha on the right flank to help Zeki Celik defensively.
On the other hand, Milan are without Antonio Mirante, Pierre Kalulu and Simon Kjaer.
According to Gazzetta, USMNT international Musah is a favourite over Bennacer, while Matteo Gabbia will partner with Fikayo Tomori in central defence. Mike Maignan has recovered from a slight muscle injury and will start in goal at the Stadio Olimpico.
Roma vs. Milan – probable line-ups
Roma (4-4-2): Svilar; Celik, Mancini, Smalling, Spinazzola; Bove, Paredes, Pellegrini; El Shaarawy, Lukaku, Dybala.
Milan (4-2-3-1): Maignan; Calabria, Gabbia, Tomori, Theo Hernandez; Musah, Reijnders; Pulisic, Loftus-Cheek, Leao; Giroud.