Milan launch a new trident attack of Noah Okafor, Samuel Chukwueze and Luka Jovic, while giant-killers Genoa are without Mateo Retegui.
It kicks off at the Stadio Luigi Ferraris, also known as Marassi, at 19.45 UK time (18.45 GMT).
Following a goalless Champions League trip to Borussia Dortmund, Stefano Pioli is missing Simon Kjaer, Ruben Loftus-Cheek, Rade Krunic, Ismael Bennacer, Pierre Kalulu and Mattia Caldara.
Olivier Giroud, Rafael Leao and Christian Pulisic are rested, so it is an exciting new trident with Okafor, Jovic and Chukwueze, while Yacine Adli returns in midfield.
Genoa have been remarkably impressive after earning promotion, beating Lazio and Roma, while holding Napoli and Udinese to thrilling 2-2 draws.
Milan Badelj and Kevin Strootman are still on the treatment table, while Retegui is not even on the bench due to a knee issue, which also ruled him out of the Italy squad.
However, Albert Gudmundsson is on spectacular form with four goals in eight games this season between Serie A and the Coppa Italia.
Ruslan Malinovskyi can also provide attacking threat, while Stefano Sabelli returns, but Junior Messias is carrying a flexor injury.
Genoa: Martinez; De Winter, Bani, Dragusin, Vasquez; Sabelli, Thorsby, Frendrup, Haps; Malinovskyi; Gudmundsson
Milan: Maignan; Florenzi, Thiaw, Tomori, Theo Hernandez; Musah, Adli, Reijnders; Chukwueze, Jovic, Okafor
Player statistic
| 21' |  |
Theo Hernández | ||
| 22' | |
Alessandro Florenzi |
| 47' | |
Yunus Musah | ||
| 62' | |
Yacine Adli | ||
| Koni De Winter | |
68' | ||
| Josep Martínez | |
86' | ||
| 87' |  |
Christian Pulisic (Assist: Yunus Musah) | ||
| Josep Martínez |  |
90+13' | ||
| 90+9' |  |
Mike Maignan | ||
| 90+11' | |
Fikayo Tomori |
Match statistic
