At the back, Adam Bogdan starts in goal and youngster Connor Randall replaces Nathaniel Clyne at right-back, while the rest of the back four remains the same.
Southampton boss Ronald Koeman names the strongest XI possible for the home side.
Tonight’s match has to be concluded this evening, meaning a draw will see the tie go to extra-time and if required penalties.
Kick off tonight is 7.45pm GMT.
Liverpool: Bogdan, Randall, Skrtel, Lovren, Moreno, Lucas, Can, Allen, Lallana, Sturridge, Origi.
Subs: Mignolet, Smith, Milner, Benteke, Firmino, Henderson, Ibe.
Southampton: Stekelenburg; Cedric, Caulker, Van Dijk, Bertrand; Clasie, Wanyama; Davis, Mané, Tadic; Pelle.
Subs: Gazzaniga, Yoshida, Long, Romeu, Martina, Ward-Prowse, Juanmi.
Referee: Robert Madley