Inter have chosen Yuto Nagatomo, Wesley Sneijder, Samuel Eto'o and Diego Milito for the miracle comeback at Schalke.
It has been called ‘an impossible task,' but the Nerazzurri will attempt to overturn their 5-2 first leg home defeat.
The holders must score at least four goals to reach the semi-final and make history, as no club has managed this turnaround in the Champions League.
Cristian Chivu is suspended following his red card in the first leg, but Lucio's ban has now expired.
Dejan Stankovic and Thiago Motta have been chosen to boost the midfield with Javier Zanetti, leaving the left-back role to Nagatomo and Esteban Cambiasso on the bench.
Goran Pandev is benched after the new system struggled to make an impact, so Leonardo returns to the classic attack with Sneijder, Eto'o and Milito. Giampaolo Pazzini is cup-tied.
Schalke have Jefferson Farfan suspended, plus the injured Klaas-Jan Huntelaar, Christoph Moritz and Christian Pander.
There were also doubts over the fitness of Angelos Charisteas with a thigh strain and Christoph Metzelder nursing a broken nose, but the defender is able to start.
17-year-old Julian Draxler does not step in to replace Farfan, so Schalke reshuffle their midfield to support Edu and Raul.
Schalke 04: Neuer; Uchida, Howedes, Metzelder, Sarpei; Baumjohann, Matip, K Papadopoulos, Jurado; Raul, Edu
Schalke bench: Schober, Plestan, Junmin, Schimitz, Charisteas, Karimi, Draxler
Inter: Julio Cesar; Maicon, Lucio, Ranocchia, Nagatomo; Zanetti, Thiago Motta, Stankovic; Sneijder; Eto'o, Milito
Inter bench: Castellazzi, Cordoba, Materazzi, Cambiasso, Kharja, Pandev, Coutinho