Milan are forced to transform as the injury crisis bites, using Franck Kessie in a more advanced role with Olivier Giroud against Patrick Cutrone’s Empoli.
It kicks off at the Stadio Castellani at 19.45 GMT.
The Rossoneri are sliding down the standings after a series of poor results, including the 1-0 home defeat to Napoli that saw them caught in second place.
Problems continued to pile up for coach Stefano Pioli, as Zlatan Ibrahimovic was ruled out by injury, joining Rafael Leao, Simon Kjaer, Ante Rebic, Pietro Pellegri, Davide Calabria and Alessandro Plizzari on the absentee list.
Theo Hernandez returned after flu symptoms, but Kessie was moved into a more advanced trequartista role behind Giroud, as Brahim Diaz has badly lost form lately.
Empoli are making their mark this season as giant-killers, with wins away to Juventus and Napoli.
They also have ex-Milan youth product Cutrone, who made no secret of how unhappy he was at being sold to Wolves.
Nicolas Haas is out for the season after knee ligament surgery.
Empoli: Vicario; Stojanovic, Romagnoli, Luperto, Parisi; Henderson, Ricci, Zurkowski; Bajrami; Cutrone, Pinamonti
Milan: Maignan; Florenzi, Tomori, Romagnoli, Theo Hernandez; Tonali, Bennacer; Messias, Kessie, Saelemaekers; Giroud