Spurs have struggled for momentum under Jose Mourinho and are without back-to-back wins since November, while Southampton have hit top form with six wins in their last eight.
Tottenham may have picked up a first win in five Premier League outings last time out, but they were far from convincing in their 2-1 victory over Norwich City.
It was a much-needed win for Mourinho's men that keeps them in the hunt for a top-four finish, sitting as they do six points off Chelsea in the final Champions League qualifying berth.
Finishing fourth is one of Mourinho's aims in his first season at the Tottenham Hotspur Stadium, along with ending the club's 12-year wait for some silverware.
The one big blot on predecessor Mauricio Pochettino's otherwise imperious record was a failure to lift any trophies, something Mourinho will be desperate to put right.
Only Liverpool and Manchester City are in better Premier League form than Southampton, who returned to winning ways in midweek with a 2-0 victory at Crystal Palace.
Whereas relegation was once a serious possibility, Ralph Hasenhuttl has transformed his side's fortunes and momentum is very much on their side heading into this all-Premier League affair.
Mourinho has only previously lost two games against an opponent in a single calendar month on one occasion. Should Hasenhuttl again come out on top this weekend, Tottenham's decision to replace Pochettino with the Portuguese will be called into question.
Southampton's FA Cup form: W
Southampton's form (all competitions): DWWWLW
Tottenham Hotspur's FA Cup form: DW
Tottenham Hotspur's form (all competitions): LDLWDW
Also in contention to feature is Erik Lamela, a player who has been directly involved in seven goals in his last six FA Cup starts - three goals of his own and four assists.
As for Southampton, Hasenhuttl has confirmed that Cedric Soares is to miss the next three weeks through injury.
Star man Ings was rested against Palace before being introduced from the bench, suggesting he should get the nod on Saturday.
Southampton possible starting lineup:
McCarthy; Danso, Stephens, Vestergaard, Bertrand; Armstrong, Ward-Prowse, Hojbjerg, Redmond; Obafemi, Ings
Tottenham Hotspur possible starting lineup:
Gazzaniga; Aurier, Alderweireld, Sanchez, Tanganga; Dier, Ndombele; Gedson, Lo Celso, Lucas; Son
We say: Southampton 1-1 Tottenham Hotspur
Since returning to the Premier League in 2012-13, Southampton have lost six of their eight FA Cup ties against fellow top-flight opponents. They may be in good form, but we are backing Tottenham to dig in and claim a draw to take the match back to North London.
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