Napoli must win away to stuttering Empoli if they are to stay in the Scudetto race, so use Victor Osimhen, Dries Mertens, Lorenzo Insigne and Hirving Lozano together.
It kicks off at the Stadio Castellani at 14.00 UK time (13.00 GMT).
Serie A Liveblog: Inc Lazio-Milan, Empoli-Napoli, Salernitana-Fiorentina
The Partenopei can say goodbye to title hopes if they fail to pick up all three points here, having managed just one draw from their last two rounds.
Kalidou Koulibaly is suspended, with Giovanni Di Lorenzo, Stanislav Lobotka and Eljif Elmas injured.
Defender Alessandro Zanoli has a stomach bug and is not 100 per cent fit either, but is able to start.
After calls to be more attack-minded, Spalletti has listened and adapted to a 4-2-3-1 formation with Insigne, Lozano and Mertens supporting Osimhen.
Empoli are without a win in 16 Serie A rounds, a new club record, during which they managed only eight points.
This is a special reunion for Empoli coach Aurelio Andreazzoli, who was Luciano Spalletti’s assistant manager for many years at both Udinese and Roma.
Lorenzo Tonelli, Riccardo Marchizza and Nicolas Haas are all long-term injury absentees.
Empoli: Vicario; Stojanovic, Luperto, Viti, Parisi; Zurkowski, Asllani, Bandinelli; Verre, Cutrone; Pinamonti
Napoli: Meret; Zanoli, Rrahmani, Juan Jesus, Mario Rui; Anguissa, Fabian Ruiz; Lozano, Mertens, Insigne; Osimhen
My favourite game. Young Italian scores two goals !!!