Inter give Andre Onana his Serie A debut in goal, with changes in defence and midfield, as Sassuolo are finding their form despite missing Domenico Berardi.
It kicks off at the Mapei Stadium at 14.00 UK time (13.00 GMT).
The Nerazzurri got back on track midweek with a Champions League victory over Barcelona, albeit amid some controversy due to a late handball incident, but in Serie A have lost four of their last six and are level on 12 points with Sassuolo.
Joaquin Correa joined the injury list with Marcelo Brozovic and Romelu Lukaku, so Edin Dzeko and Lautaro Martinez are the only choices upfront.
Kristjan Asllani steps in for Brozovic, returning Hakan Calhanoglu to his more habitual role, while there’s a reshuffle in defence including the Serie A debut of Onana in goal.
Sassuolo are without Domenico Berardi, Gregoire Defrel, Hamed Junior Traore and Mert Muldur, but still notched up back-to-back wins over Torino and Salernitana.
Armand Laurienté has been a revelation with a goal, two assists and lots of dangerous runs.
These teams have never shared the points at the Mapei Stadium in Serie A, but it’s a very high-scoring fixture with a total 31 goals in nine meetings.
Sassuolo: Consigli; Toljan, Erlic, Ferrari, Rogerio; Frattesi, Maxime Lopez, Thorstvedt; Laurienté, Pinamonti, Konradsen
Inter: Onana; D’Ambrosio, Acerbi, Bastoni; Dumfries, Barella, Asllani, Calhanoglu, Dimarco; Dzeko, Lautaro Martinez
Inzaghi must play Onana for Inter to win the game. If Handanovic to be played as starting eleven, then Inter will lose the game and that will be the end of Inzaghi era at Giusepe Meazza.