Roma start Daniele De Rossi and Kostas Manolas, but not Robin Olsen, while Porto use veteran Pepe in the Champions League Round of 16.
The first leg kicks off at the Stadio Olimpico at 20.00 GMT.
The Giallorossi reached the semi-final last season and are hoping for another strong run, but have bad memories of Porto, having been knocked out twice before, most recently in the August 2016 preliminary round.
That tie saw a 1-1 draw in Portugal wiped out by Porto’s 3-0 victory in the Eternal City, aided by Daniele De Rossi and Emerson Palmieri red cards.
De Rossi has shaken off that recurring knee injury and is in the starting XI with Bryan Cristante and Lorenzo Pellegrini, while Nicolò Zaniolo and Stephan El Shaarawy flank Edin Dzeko.
Manolas has also recovered from a muscular issue to start, but Robin Olsen is only fit for the bench with his calf problem, so Antonio Mirante is handed the gloves.
Cengiz Under, Patrik Schick, Diego Perotti and late addition Rick Karsdorp are out injured, all of them with muscular issues.
Porto have their own fair share of problems, because top scorer Moussa Marega is out until March with a thigh strain.
Striker Vincent Aboubakar also misses out, but Jesus Corona sits out a self-imposed ban.
That’s because he purposefully got booked against Schalke for time-wasting to get his suspension out of the way in the final – futile – group game against Galatasaray.
He made it so obvious that UEFA took action and extended his ban to two matches rather than one.
Veteran defender Pepe and ex-Real Madrid goalkeeper Iker Casillas provide plenty of experience to the side, along with former Inter full-back Alex Telles.
Midfielder Hector Herrera has repeatedly been linked with a move to Serie A, including for Roma, as his contract is due to expire in June.
Yacine Brahimi therefore leads the trident attack with Otavio and Tiquinho Soares, but Oliver Torres is benched in favour of Fernando.
Porto are still top of Liga NOS, one point in front of Benfica, but have drawn their last two games.
They are also unbeaten in the Champions League so far this season, drawing the first and winning five, with at least three goals scored in each of the last four group matches.
It’s a return to the Olimpico for Coach Sergio Conceicao, who played for Lazio from 1998-2000.
Roma: Mirante; Florenzi, Manolas, Fazio, Kolarov; Cristante, De Rossi, Pellegrini; Zaniolo, Dzeko, El Shaarawy
Roma bench: Olsen, Juan Jesus, Marcano, Santon, Nzonzi, Pastore, Kluivert
Porto: Casillas; Eder Militao, Pepe, Felipe, Telles; Herrera, Danilo Pereira, Fernando; Otavio, Soares, Brahimi
Porto bench: Vana, Hernani, Maxi Pereira, Bruno Costa, Hernani, Adrian Lopez, Andre Pereira, Oliver Torres
Ref: Makkelie (NED)