Vlad Chiriches gets his first appearance of the season for Napoli, with Simone Verdi, Adam Ounas, Lorenzo Insigne and Dries Mertens against FC Zurich.
The Europa League Round of 32 tie kicks off at the Stadio San Paolo at 17.55 GMT.
The Partenopei won the first leg 3-1 in Switzerland and are in a very strong position to progress, but as usual, they failed to keep a clean sheet and conceded an unnecessary late goal.
Carlo Ancelotti shakes things up in the absence of Raul Albiol and Mario Rui, so Romania international Chiriches makes his first appearance of the season for Napoli.
He has been out of action since tearing his anterior cruciate ligament in a Nations League match in early September, but is thrown straight into the starting XI.
Insigne plays, as he is suspended this weekend in Serie A against Parma, and is partnered by Dries Mertens, with Verdi and Ounas allowing Jose Callejon and Allan to rest, moving Piotr Zielinski to central midfield.
FC Zurich made the trip without suspended Hekuran Kryeziu, but Benjamin Kololli showed his confidence and skill when scoring with a Panenka-style chipped penalty in the first leg.
Assan Ceesay and Stephen Odey provide pace in attack.
Napoli have lost only one of their last 14 European home fixtures, 3-1 to RB Leipzig.
Kalidou Koulibaly, Nikola Maksimovic and Mario Rui are all one yellow card away from suspension in the Europa League.
Napoli: Meret; Hysaj, Chiriches, Koulibaly, Ghoulam; Ounas, Diawara, Zielinski, Verdi; Insigne, Mertens
Napoli bench: Ospina, Luperto, Malcuit, Maksimovic, Allan, Callejon, Milik
FC Zurich: Brecher; Winter, Bangura, M Kryeziu, Kololli; Khelifi, Sohm, Domgjoni, Schonbachler; Odey, Ceesay
Zurich bench: Vanins, Maxso, Kharabadze, Krasniqi, Dixon, Zumberi, Kasai
Ref: Sidiropoulos (GRE)
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