Roma face a grueling three games in six days before the Champions League semi-final first-leg clash against Liverpool at Anfield on Tuesday.
The Giallorossi successfully navigated their way past Genoa on Wednesday, beating the visitors 2-1.
Turkey international Cengiz Under returned, making his first start in four games and scored the opener.
Roma still have to take on SPAL on Saturday away from home before traveling to England.
Di Francesco cannot afford to field a reserve side as a top-four spot has not been guaranteed yet.
The Roma boss has however, dropped a few hints regarding how his team selection will look ahead of the Liverpool clash.
During his pre-match press conference, Di Francesco revealed that Aleksandar Kolarov would miss the SPAL game, while Cengiz Under and Edin Dzeko could be rested.
“This game against SPAL is very important for lots of reasons. We must make sure we capitalise on the chances that come our way,” he said.
“Diego Perotti is OK and he’ll be in the squad. Aleksandar Kolarov won’t be coming with us this weekend, though—he has a minor muscle complaint.
“Edin Dzeko is really up for it right now but I’ll speak to him and decide whether or not to start him tomorrow. If not, Patrik Schick will lead the line.
“As for who will come in for Kolarov at left-back tomorrow, it will be a left-footed player. Jonathan Silva is more likely than Luca Pellegrini.
“Cengiz Under’s pace is a vital part of his game so we need to make sure he doesn’t suffer from fatigue when there are so many games. We won’t rest everyone.
“Lorenzo Pellegrini could well start—I’m undecided between him and another player.”
Perotti has only recently recovered from a calf injury, Di Francesco could be giving him a run out to gain match fitness.
Manolas was rested against Genoa due to an injury problem but has recovered and should be ready for the Liverpool game.
The Argentinian is likely to get the nod against Liverpool as is Under, Dzeko and Kolarov – if he is fit.
Therefore we could have a Roma starting line-up looking something like this:
Roma Predicted XI: Alisson, Kolarov, Fazio, Manolas, Florenzi, De Rossi, Strootman, Nainggolan, Perotti, Cengiz Under, Dzeko