Milan make changes with Fode Ballo-Toure coming in, Rade Krunic joining Brahim Diaz, Rafael Leao and Zlatan Ibrahimovic, while Inter look to Edin Dzeko, Lautaro Martinez and Hakan Calhanoglu.
The Derby della Madonnina kicks off at the Stadio Giuseppe Meazza, in San Siro, at 19.45 GMT.
You can follow all the build-up and action as it happens on the LIVEBLOG.
This is not only a Milan Derby between bitter rivals, but also a head-to-head at the top of the table between first and third.
It also has extra spice this season, as Calhanoglu faces his former club for the first time since leaving as a free agent to cross the city.
Theo Hernandez is suspended, with Alessio Romagnoli, Mike Maignan, Samu Castillejo, Junior Messias and Alessandro Plizzari injured.
Stefano Pioli therefore brings in Ballo-Toure at left-back, but drops Alexis Saelemaekers, using Krunic, Brahim Diaz and Leao together in support of Ibrahimovic.
As for Inter, Simone Inzaghi has a full squad to choose from and confidence growing after the midweek Champions League victory over Sheriff.
Calhanoglu gets the nod against his old club, with Ivan Perisic and Matteo Darmian on the wings.
Lautaro Martinez and Edin Dzeko are the first-choice front two, with Joaquin Correa and Alexis Sanchez on the bench.
Milan: Tatarusanu; Calabria, Kjaer, Tomori, Ballo-Toure; Tonali, Kessie; Krunic, Brahim Diaz, Leao; Ibrahimovic
Inter: Handanovic; Skriniar, De Vrij, Bastoni; Darmian, Barella, Brozovic, Calhanoglu, Perisic; Lautaro Martinez, Dzeko