Napoli aim to end their crisis and throw everything they’ve got at Michael Essien and Adel Taarabt’s reworked Milan.
It kicks off at the Stadio San Paolo at 19.45 GMT, click here for a match preview.
Neither side is going through a great period of form, as Rafa Benitez’s men were humiliated 3-0 by Atalanta and then lost 3-2 midweek to Roma in the Coppa Italia semi-final.
Anthony Reveillere has joined the injury list with Juan Camilo Zuniga and Giandomenico Mesto, but Henrique is on the bench for the first time after his paperwork came through from Palmeiras.
Gonzalo Higuain leads the way with support from Marek Hamsik, Dries Mertens and Lorenzo Insigne, so Jose Maria Callejon gets a rare rest.
Faouzi Ghoulam and Jorginho both start following their January transfers, while Pepe Reina is glad to see Mario Balotelli again, having become the first goalkeeper to save his penalty.
Milan are unbeaten in Serie A under Coach Clarence Seedorf, though the run of two consecutive victories was halted by a 1-1 draw with Torino last week.
Balotelli returns from suspension, but Daniele Bonera is now on the naughty step.
Long-term absentees include Stephan El Shaarawy, Cristian Zapata, Valter Birsa and Bryan Cristante, while Keisuke Honda is ruled out by gastroenteritis.
Essien gets his Serie A debut in midfield with Nigel De Jong, while Ignazio Abate was given a new role in the attacking trio behind Balotelli.
Ricky Kaka has been suffering from flu over the last few days, so is not fit to start. Adel Taarabt also makes his debut after completing the loan move from QPR.
Milan haven’t beaten Napoli in their last five encounters, earning just three draws.
Napoli: Reina; Maggio, Fernandez, Albiol, Ghoulam; Inler, Jorginho; Mertens, Hamsik, Insigne; Higuain
Napoli bench: Rafael, Colombo, Uvini, Henrique, Britos, Behrami, Dzemaili, Radosevic, Pandev, Callejon, Duvan Zapata
Milan: Abbiati; De Sciglio, Mexes, Rami, Emanuelson; De Jong, Essien; Abate, Taarabt, Robinho; Balotelli
Milan bench: Amelia, Gabriel, Constant, Silvestre, Zaccardo, Montolivo, Poli, Muntari, Saponara, Kaka, Petagna, Pazzini