Roma give Tommaso Baldanzi his first start with Romelu Lukaku and Stephan El Shaarawy, while Frosinone look to Matias Soule and Kaio Jorge.
It kicks off at the Stadio Stirpe at 17.00 GMT.
The Giallorossi were in action in Rotterdam on Thursday with a creditable 1-1 Europa League play-off draw against Feyenoord.
They now face pressure to keep up in the race for a European position in Serie A, having suffered their first defeat under coach Daniele De Rossi against leaders Inter.
Tammy Abraham is the only remaining injury absentee, as Chris Smalling is on the bench.
Dybala is rested after starting five games in a row, so January signing Baldanzi makes his full debut.
Surprisingly, Mile Svilar is confirmed in goal rather than Rui Patricio, who tends to start in Serie A.
Frosinone have Simone Romagnoli suspended and a long injury list, including Fares Ghedjemis, Nadir Zortea, Riccardo Marchizza, Anthony Oyono, Kevin Bonifazi and Mateus Lusuardi.
They managed only one point from the last three rounds, losing 5-1 to Fiorentina.
Frosinone: Turati; Lirola, Monterisi, Okoli, Valeri; Brescianini, Mazzitelli; Gelli, Soulé, Kaio Jorge; Reinier
Roma: Svilar; Kristensen, Mancini, Huijsen, Angelino; Cristante, Paredes, Baldanzi; Azmoun, El Shaarawy; Lukaku
Player statistic
| 38' |  |
Dean Huijsen (Assist: Gianluca Mancini) | ||
| 39' |  |
Dean Huijsen |
| 66' | |
Gianluca Mancini | ||
| 71' | |
Sardar Azmoun | ||
| 76' | |
Sardar Azmoun | ||
| 81' |  |
Leandro Paredes |
Match statistic
