Danny Ings scored the all-important goal on New Year’s Day to give Saints a 1-0 win when the two sides last met. Spurs are not taking the FA Cup lightly and Mourinho is expected to field a strong starting line-up.
Ralph Hasenhuttl’s side are on a brilliant run of form having lost just one game out of last eight in all competitions. The Saints are heading into this game on the back of a 2-0 win against Crystal Palace in the Premier League and should be high on confidence.
Spurs picked up their first win in the Premier League since Boxing Day when they won 2-1 against Norwich City in their previous game.
Hugo Lloris started against the Canaries, but Mourinho could start with Paulo Gazzaniga for the cup game.
In defence, Davinson Sanchez is likely to get a chance alongside Toby Alderweireld. The Colombian hasn’t been used since his poor display against Middlesbrough.
Japhet Tanganga was dropped in the midweek after starting the previous three games. He is likely to take the left-back role, with Ryan Sessegnon likely to be pushed further up the pitch.
With Harry Winks picking up an injury, Mourinho could make as many as three changes in the midfield, and Eric Dier, Tanguy Ndombele and Gedson Fernandes all could be involved. Dier, 26, played the last 34 minutes against Norwich, and he is likely to start in midfield rather than in defence.
Predicted Spurs XI vs Southampton: Gazzaniga, Alderweireld, Sanchez, Aurier, Tanganga, Dier, Fernandes, Ndombele, Sessegnon, Alli, Son.