Napoli ring the changes with Giacomo Raspadori, Giovanni Simeone and Bartosz Bereszynski in the Coppa Italia, as Cremonese make their debut under new coach Davide Ballardini.
It kicks off at the Stadio Diego Armando Maradona at 20.00 GMT and the winners go on to face Roma in the quarter-final.
You can follow all the build-up and action as it happens on the LIVEBLOG.
There had been some concerns as to whether the match would go ahead after gale-force winds and storms hit the region, knocking down scaffolding and trees, but an inspection this afternoon gave the go-ahead.
The Partenopei are buzzing after their 5-1 demolition of rivals Juventus to send them nine points clear at the top of the Serie A table.
Hirving Lozano is suspended for this match, while Luciano Spalletti rotates the squad, giving Giacomo Raspadori and Giovanni Simeone the opportunity to shine.
There is also the full debut of ex-Sampdoria defender Bartosz Bereszynski, who arrived in the January transfer window.
Diego Demme is on paternal leave, as his partner gave birth this morning, so Gianluca Gaetano is tested as a deep-lying playmaker.
Cremonese sacked Massimiliano Alvini after failing to win a single Serie A match this season, sitting rock bottom on seven points.
He was replaced by Davide Ballardini at the weekend and makes his debut on the bench here.
There are a lot of problems to deal with, missing the likes of Vlad Chiriches, Cyriel Dessers, Gonzalo Escalante, Paolo Ghiglione, Ionut Radu, Luka Lochoshvili and Christian Acella.
He therefore starts Daniel Ciofani with David Okereke.
Napoli: Meret; Bereszynski, Ostigard, Juan Jesus, Olivera; Ndombele, Gaetano; Elmas; Raspadori, Simeone, Zerbin
Cremonese: Carnesecchi; Vasquez, Bianchetti, Hendry; Sernicola, Pickel, Meite, Castagnetti, Quagliata; Ciofani, Okereke