Inter replace suspended Nicolò Barella with Arturo Vidal, while Lautaro Martinez partners Edin Dzeko against Liverpool’s Mohamed Salah, Sadio Mané and Diogo Jota.
The first leg of the Champions League Round of 16 kicks off at San Siro at 20.00 GMT.
You can follow all the build-up and action as it happens on the LIVEBLOG.
The away goals rule has been abolished this season, so that could also change the approach teams take in two-legged ties.
The stadium is only open at 50 per cent capacity due to COVID-19 regulations, although only those with vaccines and a medical-grade mask can enter.
Barella is suspended, with Joaquin Correa and Robin Gosens injured, but Alessandro Bastoni has recovered from an ankle knock and takes his place in defence.
Vidal is picked to stand in for Barella, with Denzel Dumfries and Ivan Perisic on the wings, while Lautaro Martinez beats Alexis Sanchez to the punch alongside Edin Dzeko.
Liverpool have been dominant in the Champions League so far this season, winning all six of their group games, including home and away against Inter’s city rivals Milan.
Inter took their time to get going, but won three in a row until the slender defeat to Real Madrid to secure qualification for the Round of 16 for the first time in 10 years.
Jurgen Klopp brought in Luis Diaz during the January transfer window and has a full squad to choose from.
Diogo Jota nonetheless gets the nod upfront with Mané and former Roma and Fiorentina star Mohamed Salah.
Ex-Roma goalkeeper Alisson Becker has been a rock for the Reds.
Jordan Henderson is dropped for Harvey Elliott, with Ibrahima Konate in defence.
Inter: Handanovic; Skriniar, De Vrij, Bastoni; Dumfries, Vidal, Brozovic, Calhanoglu, Perisic; Dzeko, Lautaro Martinez
Liverpool: Alisson; Alexander-Arnold, Konaté, Van Dijk, Robertson; Fabinho, Thiago Alcantara, Elliott; Salah, Diogo Jota, Mané