Napoli need a victory to close in on the Champions League spots, but host a Milan side in crisis at the San Paolo.
It kicks off at 19.45 UK time (18.45 GMT), follow all the action as it happens on our LIVEBLOG.
The Partenopei would go within four points of third-placed Lazio with a win here tonight, as the Aquile were pegged back 1-1 by Atalanta.
It’d also sit Napoli only five points from Roma, who have leapfrogged into second spot.
However, Rafa Benitez must keep an eye on Thursday’s Europa League semi-final with Dnipro and recover confidence after a shock 4-2 defeat to Empoli midweek.
Jose Callejon and Lorenzo Insigne get the chance to work on their impressive partnership, joined by Marek Hamsik and Gonzalo Higuain.
Milan were also humiliated by minnows on Wednesday night, losing 3-1 at home to Genoa.
They go into this game mid-table, distracted by negotiations to sell half the club and with a decimated squad.
Jeremy Menez, Philippe Mexes and Ignazio Abate sit out bans, while Suso, Adil Rami, Luca Antonelli, Stephan El Shaarawy, Riccardo Montolivo and Michael Essien are injured.
Mattia Destro is given a rare chance to play as a genuine centre-forward, supported by Keisuke Honda and Giacomo Bonaventura.
Milan beat Napoli in December and that was probably the high point of their campaign, but it’s been all downhill since.
The Rossoneri have won at the San Paolo only twice in the last 19 years, both 2-1 results in January 1998 and October 2010.
Napoli: Andujar; Maggio, Albiol, Britos, Ghoulam; Jorginho, David Lopez; Callejon, Hamsik, Insigne; Higuain
Napoli bench: Rafael, Colombo, Henrique, Koulibaly, Strinic, Gargano, Inler, Mesto, Mertens, Gabbiadini, Duvan Zapata
Milan: Diego Lopez; De Sciglio, Alex, Paletta, Bocchetti; Poli, De Jong, Van Ginkel; Honda, Destro, Bonaventura
Milan bench: Abbiati, Donnarumma, Albertazzi, Paletta, Zaccardo, Zapata, Felicioli, Gamarra, Cerci, Pazzini, Di Molfetta