Milan transform with Tammy Abraham and Alvaro Morata upfront, while Inter seek a seventh straight Derby della Madonnina victory with Lautaro Martinez and Marcus Thuram.
It kicks off at San Siro at 19.45 UK time (18.45 GMT).
You can follow all the build-up and action as it happens from today’s Serie A games on the LIVEBLOG.
The Rossoneri are in crisis after one win in five competitive matches this season, falling to a 3-1 Champions League defeat against Liverpool midweek, which put coach Paulo Fonseca on the chopping block already.
You can join Football Italia for the build-up to this huge fixture with our YouTube Channel transmitting from San Siro and New York City.
Davide Calabria joined Malick Thiaw, Ismael Bennacer, Marco Sportiello and Alessandro Florenzi on the treatment table.
Mike Maignan limped off against Liverpool, but has recovered from a knock to start in goal.
The big changes are tactical, moving to a 4-4-2 with Abraham and Morata together upfront, dropping Ruben Loftus-Cheek to the bench.
Strahinja Pavlovic is also replaced by Matteo Gabbia.
Inter have drawn their last two games against Monza and Manchester City, but are seeking a record seventh straight Derby della Madonnina victory.
Federico Dimarco is back after a muscular issue forced him to miss the Champions League trip to the Etihad.
Lautaro Martinez and Henrikh Mkhitaryan were substitutes in that game, but start here this evening.
Inter vs. Milan line-ups
Inter: Sommer; Pavard, Acerbi, Bastoni; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Thuram, Lautaro Martinez
Milan: Maignan; Emerson Royal, Gabbia, Tomori, Theo Hernandez; Pulisic, Fofana, Reijnders; Leao; Morata, Abraham
Player statistic
| 10' |  |
Christian Pulisic | ||
| Henrikh Mkhitaryan |  |
18' | ||
| Federico Dimarco (Assist: Lautaro Martínez) |
|
27' | ||
| 38' | |
Youssouf Fofana | ||
| Hakan Calhanoglu | |
40' |
