The Netherlands international, who only made the bench for Sunday's derby against AC Milan, will take up his usual trequartista role behind lone striker Luc CastaignosWesley Sneijder will start for Inter in Thursday night's Coppa Italia clash with Genoa at San Siro.
The Netherlands international, who has only just recovered from a muscular problem which had sidelined him since November, only made a late cameo in the Derby della Madonnina on Sunday but he returns in his usual trequartista role.
With Diego Milito on the bench and Giampaolo Pazzini rested, Luc Castaignos will lead the line for the Nerazzurri, while there are also starts for Davide Faraoni, Andrea Poli, and Joel Obi alongside Esteban Cambiasso in midfield.
Ivan Cordoba and Andrea Ranocchia have been paired together at the heart of the defence, while Luca Castellazzi takes over in goal from Julio Cesar.
As for Genoa, new Genoa boss Pasquale Marino has also named a much-changed line-up, with recent arrival Alberto Gilardino and Rodrigo Palacio, who scored the winner against Udinese at the weekend, among the most notable absentees.
Inter (4-4-1-1): Maicon, Cordoba, Ranocchia, Zanetti; Faraoni, Cambiasso, Poli, Obi; Sneijder; Castaignos
Subs: Orlandoni, Lucio, Thiago Motta, Alvarez, Milito, Zarate, Nagatomo
Genoa (4-3-1-2): Lupatelli; Sampirisi, Granqvist, Moretti, Rossi; Kucka, Seymour, Brisa; Jorquera; Pratto, Ze Eduardo
Subs: Scarpi, Jankovic, Mesto, Constant, Marchiori, Sculli, Biondini