The north London club have made a stuttering start to the season, having won just once in their last seven games in all competitions.
Mauricio Pochettino’s side are winless in their last three games, including a penalty-shoot defeat against Colchester in the EFL Cup clash on Tuesday.
Spurs also suffered a 2-1 defeat against Leicester City in their last Premier League game and drew 2-2 against Olympiakos in the Champions League. It shows they badly need to bounce back.
Pochettino fielded a strong team against Colchester in the midweek, and the Argentine is expected to change the entire squad for the Premier League clash against his former club.
It means Hugo Lloris will be back in goal in front of the defensive backline of Serge Aurier, Toby Alderweireld, Jan Vertonghen, and Danny Rose.
Harry Winks has been brilliant this season, and the 23-year-old is expected to start in midfield, alongside summer signing Tanguy Ndombele.
Harry Kane is expected to replace Troy Parrott up front, while the likes of Son Heung-Min, Erik Lamela, and Christian Eriksen should return to the squad.
Here’s the predicted Spurs starting XI vs Southampton: Lloris, Aurier, Alderweireld, Vertonghen, Rose, Winks, Ndombele, Lamela, Son, Eriksen, Kane.