Roma go with Lorenzo Pellegrini supporting Tammy Abraham and Andrea Belotti, benching Nicolò Zaniolo, while Dejan Stankovic reshuffles rock-bottom Sampdoria.
It kicks off at the Stadio Luigi Ferraris in Genoa at 17.30 UK time (16.30 GMT).
The Giallorossi kept their Europa League hopes alive with a 1-1 draw away to Real Betis on Thursday, and have the opportunity to leapfrog Lazio and Udinese into fourth place with a third consecutive Serie A victory.
Injuries remain a problem, making the trip to Marassi without Paulo Dybala, Zeki Celik, Marash Kumbulla, Georginio Wijnaldum and Ebrima Darboe.
Zaniolo was suspended in the Europa League, so is well-rested, but is still dropped to the bench as the two-striker pairing of Abraham and Belotti is started for only the second time.
Stephan El Shaarawy is a new addition as a left-sided wing-back.
Sampdoria sacked Marco Giampaolo after just two points from eight Serie A rounds, so Dejan Stankovic was brought in and earned a 1-1 draw with Bologna on his debut.
This will be an intriguing clash between Jose Mourinho, who won the Treble at Inter, with one of the midfielders who proved so instrumental in that squad.
Jeison Murillo joined Harry Winks and Manuel De Luca on the absentee list, but there’s an opportunity for former Roma flop Gonzalo Villar, who is currently on loan with an option to buy for €8m.
The Blucerchiati have only managed one win in their last eight Serie A meetings with Roma, along with two draws and five losses.
Sampdoria: Audero; Bereszynski, Ferrari, Colley, Augello; Leris, Rincon, Villar, Djuricic; Gabbiadini, Caputo
Roma: Rui Patricio; Mancini, Smalling, Ibanez; Zalewski, Cristante, Camara, El Shaarawy; Pellegrini; Belotti, Abraham