Milan hope to build on recent form with Carlos Bacca, but Riccardo Saponara is eager to make his old club pay in Empoli.
It kicks off at the Stadio Castellani at 19.45 GMT, follow the action as it happens on our LIVEBLOG.
Sinisa Mihajlovic has been under pressure since the moment he arrived, but reaching the Coppa Italia semi-finals and beating Fiorentina 2-0 last week took the edge off.
He has Luiz Adriano back in the squad after the transfer to Jiangsu Suning was called off, while Mario Balotelli is also on the bench after four months out injured.
With Jeremy Menez, Rodrigo Ely, Philippe Mexes and Diego Lopez sidelined, Bacca again leads the attack with M’Baye Niang.
Jack Bonaventura and a revitalised Keisuke Honda take the wings.
Empoli are only one point behind Milan and recently put together a club record four consecutive victories.
They also play some of the most impressive football in Italy, as Marco Giampaolo continued the good work started by Maurizio Sarri.
Saponara is a key figure and will be very eager to make his mark against the club that failed to give him a real chance.
Leandro Paredes is suspended in midfield and a major loss for Empoli, but Piotr Zielinski is a talent to watch.
Veteran hitman Massimo ‘Big Mac’ Maccarone is still banging the goals in and is partnered by Manuel Pucciarelli.
Empoli: Skorupski; Laurini, Tonelli, Barba, Mario Rui; Zielinski, Masiello, Buchel; Saponara; Maccarone, Pucciarelli
Empoli bench: Pugliesi, Pelagotti, Zambelli, Cosic, Camporese, Bittante, Diousse, Krunic, Croce, Piu, Livaja, Mchedlidze
Milan: Donnarumma; Abate, Alex, Romagnoli, Antonelli; Honda, Montolivo, Bertolacci, Bonaventura; Niang, Bacca
Milan bench: Abbiati, Livieri, De Sciglio, Calabria, Zapata, De Jong, Poli, Kucka, Jose Mauri, Luiz Adriano, Boateng, Balotelli