Milan are decimated by bans and injuries, so Gianluca Lapadula and Lucas Ocampos start against troubled Genoa with Adel Taarabt.
It kicks off at San Siro at 19.45 GMT, follow the build-up and action as it happens on the LIVEBLOG.
The Rossoneri are in the running for Europe, but are still smarting from last week’s controversial 2-1 defeat to Juventus.
Their reaction to the last-gasp Paulo Dybala penalty proved costly, as Carlos Bacca was given a one-match ban for insulting the referee.
Jose Ernesto Sosa was sent off in that game, and is therefore also suspended, along with Alessio Romagnoli.
Suso, Ignazio Abate, Jack Bonaventura and Riccardo Montolivo are injured, so Lapadula gets a rare start along with Gerard Deulofeu and Ocampos, who arrived on loan from Genoa in January.
Juraj Kucka and Andrea Bertolacci also get to face their former club.
Genoa are in dire straits, with just one victory since mid-December (against struggling Empoli) and above all are fresh from a humiliating Derby della Lanterna defeat.
It’s the first time in 57 years that Sampdoria have won both Serie A editions of the derby in a single season.
Nicolas Andre Burdisso is suspended in defence, while Mattia Perin, Miguel Veloso and Nikola Ninkovic are on the treatment table.
There’s a very familiar face, as Adel Taarabt gets to start at San Siro in a Genoa jersey, after his brief six-month spell at Milan.
He completes the attack with Giovanni Simeone and Darko Lazovic.
Milan: Donnarumma; De Sciglio, Zapata, Paletta, Vangioni; Kucka, Bertolacci, Mati Fernandez; Ocampos, Lapadula, Deulofeu
Milan bench: Storari, Plizzari, Honda, Gomez, Poli, Antonelli, Cutrone, Locatelli, Pasalic, Calabria
Genoa: Lamanna; Izzo, Munoz, Gentiletti, Laxalt; Hiljemark, Cataldi, Ntcham; Lazovic, Simeone, Taarabt
Genoa bench: Rubinho, Edenilson, Cofie, Palladino, Biraschi, Beghetto, Orban, Pandev, Brivio, Rigoni, Morosini, Pinilla