Olivier Giroud, Rafael Leao and Brahim Diaz lead the way for Milan with Tommaso Pobega in for suspended Sandro Tonali, as Lecce start Rossoneri-owned striker Lorenzo Colombo.
It kicks off at the Stadio Via del Mare at 17.00 GMT.
The Rossoneri are in dire need of a boost after a disappointing couple of matches, as they fumbled a 2-0 lead in the final minutes for a 2-2 draw with Roma, then were eliminated from the Coppa Italia midweek by 10-man Torino in extra time.
The tension is already on with the Supercoppa coming up against rivals Inter in Riyadh on Wednesday.
Tonali is suspended, joining Mike Maignan, Ante Rebic, Rade Krunic, Fode Ballo-Toure, Alessandro Florenzi and Zlatan Ibrahimovic on the treatment table.
Simon Kjaer and Divock Origi are back on the bench after injuries, while Tommaso Pobega is preferred to Aster Vranckx in the Tonali role.
Lecce are on fine form, amassing 11 points in the last five rounds, including victories here over Atalanta and Lazio.
Colombo is particularly eager to impress against his parent club, while Hjulmand is back from suspension.
Only Kastriot Dermaku and Marin Pongracic are still out of action.
Lecce: Falcone; Gendrey, Baschirotto, Umtiti, Pezzella; Blin, Hjulmand, Gonzalez; Strefezza, Colombo, Di Francesco
Milan: Tatarusanu; Calabria, Kalulu, Tomori, Theo Hernandez; Bennacer, Pobega; Saelemaekers, Brahim Diaz, Leao; Giroud