The Brazil international makes his first appearance since the 2-2 draw against Manchester City at the end of August, with Jonjo Shelvey also coming into the midfield
The Brazil international, who was sidelined for a large chunk of the 2011-12 campaign, picked up the latest problem in the 2-2 draw against Manchester City at the end of August.
Jordan Henderson drops to the bench after the Reds' midweek defeat to Tottenham to make way for the returning Lucas, while Stewart Downing is also on the bench, with Jose Enrique retreating to left-back.
That opens up a space for Jonjo Shelvey to start in support of striker Luis Suarez, who continues alongside Raheem Sterling.
Southampton boss Nigel Adkins names an unchanged side to the XI that drew with Norwich City in the midweek, with Gaston Ramirez continuing in support of Rickie Lambert in attack.
Liverpool starting XI: Reina; Johnson, Skrtel, Agger, Enrique; Lucas, Allen, Gerrard; Shelvey, Suarez, Sterling.
Subs: Jones, Carragher, Sahin, Henderson, Downing, Suso, Wisdom.
Southampton starting XI: Gazzaniga; Clyne, Yoshida, Fonte, Shaw; Puncheon, Schneiderlin, Cork, Lallana; Ramirez, Lambert.
Subs: Kelvin Davis, Ward-Prowse, Rodriguez, Mayuka, Steven Davis, Reeves, Hooiveld.