Milan need a victory to consolidate top spot and look to Olivier Giroud, Brahim Diaz and Rafael Leao, while Fiorentina target Europe with Arthur Cabral and Riccardo Saponara.
It kicks off at a sold out San Siro at 14.00 UK time (13.00 GMT).
Serie A Liveblog: Juventus-Venezia, Milan-Fiorentina, Udinese-Inter, Roma-Bologna
The Rossoneri are in control of their destiny for the first time, as Inter lost the game in hand with Bologna and are now two points behind the leaders.
It’s technically three points, as Stefano Pioli’s men also have a superior head-to-head record.
Ismael Bennacer is only fit for the bench, with Simon Kjaer and Alessandro Florenzi out of action, so Franck Kessie drops back into midfield, leaving Brahim Diaz the trequartista position.
Fiorentina also played their game in hand on Wednesday and suffered a shock 4-0 home defeat to Udinese, so need to shake that off.
Alvaro Odriozola has joined Gaetano Castrovilli on the treatment table, with Arthur Cabral taking back the centre-forward role.
Giacomo Bonaventura and Lucas Torreira are only fit for the bench.
Milan: Maignan; Calabria, Kalulu, Tomori, Theo Hernandez; Tonali, Kessie; Messias, Brahim Diaz, Leao; Giroud
Fiorentina: Terracciano; Venuti, Milenkovic, Igor, Biraghi; Duncan, Amrabat, Maleh; Nico Gonzalez, Cabral, Saponara