Inter rely on Lautaro Martinez and Edin Dzeko upfront, knowing a win over Roberto De Zerbi’s Shakhtar Donetsk should guarantee Champions League progress.
It kicks off at San Siro at 17.45 GMT.
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The Nerazzurri could book their spot in the Round of 16 this evening, as long as they win and Real Madrid avoid defeat to Sheriff.
It would be the first time Inter have made it into the Champions League knockouts for a decade.
Their last three meetings with Shakhtar Donetsk ended 0-0, but before that Inter thrashed them 5-0 in the one-off Europa League semi-final of August 2020.
It is also fair to point out that Inter hit the woodwork three times in the last two encounters.
Alexis Sanchez and Stefan de Vrij are still out of action, but Dzeko is chosen ahead of Joaquin Correa to partner Lautaro Martinez upfront.
Andrea Ranocchia again fills in the back three, with Hakan Calhanoglu, Nicolò Barella and Marcelo Brozovic providing the core midfield.
Shakhtar Donetsk have struggled in the Champions League under former Sassuolo and Benevento coach De Zerbi, managing only one point, a 0-0 home draw with Inter.
They made the trip without Alan Patrick, Georgiy Sudakov, Ismaily and Lassina Traore, leaving only two available strikers.
Marlon followed De Zerbi from Sassuolo to Ukraine over the summer.
Inter: Handanovic; Skriniar, Ranocchia, Bastoni; Darmian, Barella, Brozovic, Calhanoglu, Perisic; Lautaro Martinez, Dzeko
Inter bench: Cordaz, Radu, Dumfries, Gagliardini, Vecino, Kolarov, Sensi, Correa, Vidal, Dimarco, D’Ambrosio
Shakhtar Donetsk: Trubin; Dodo, Vitao, Marlon, Matviyenko; Tete, Stepanenko, Maycon; Pedrinho, Fernando, Solomon
Shakhtar bench: Shevchenko, Pyatov, Kryvtsov, Marcos Antonio, Marlos, Bondarenko, Mudryk, Konoplia, Korniienko, Sikan, Konoplyanko, Bondar
Ref: Hategan (ROU)