Serge Aurier makes his first league start since being sent off in the win away at West Ham United last month as Mauricio Pochettino sticks to his promise of a tactical surprise and benches midfielder Eric Dier.
Aurier seemingly starts at left-back to deal with the electrifying pace of Liverpool winger Mohamed Salah, who has made a flying start to his Anfield career with eight goals in all competitions.
Returning left-back Ben Davies - back from illness - can only make the bench, with Kieran Trippier starting at right-back.
Elsewhere Toby Alderweireld makes his 100th Spurs appearance, joining club-record summer signing Davinson Sánchez and Jan Vertonghen centrally.
Striker Harry Kane - who scored 11 goals in all competitions in September but has yet to net in October - starts up top, backed by his usual support cast of Dele Alli, Heung-min Son and Christian Eriksen.
Alli could start in a deeper central midfield role with Eriksen and Son either side of Kane.
Spurs' midfield pair Mousa Dembélé and Victor Wanyama both miss out due to hip and knee injuries, with Harry Winks starting for the third successive match after fine displays against Bournemouth and Real Madrid.
For Liverpool, James Milner is rewarded for his fine performance in their 7-0 Champions League thrashing of Maribor on Tuesday with a start, joining captain Jordan Henderson and Emre Can.
He replaces Georginio Wijnaldum, who is missing from the match-day squad entirely with a knee injury sustained in training. His absence allows Marko Grujić to make the bench for only the third time this term.
The other change from their draw to Manchester United last weekend sees Trent Alexander-Arnold benched in favour of Joe Gomez at right-back.
Simon Mignolet also displaces Loris Karius in goal, the German goalkeeper having been chosen as the club's European 'keeper this term but playing second-fiddle to his Belgian counterpart in the league.
Salah, Philippe Coutinho and Roberto Firmino - all of whom scored in mid-week - make up a dangerous front-three for the visitors.
Sadio Mané - who scored two goals in the last meeting between these two teams back in February - misses out due to a hamstring injury while long-term absentees Adam Lallana (thigh) and Nathaniel Clyne (back) remain unavailable.
Both sides rotated somewhat in mid-week for their respective Champions League clashes and welcome back some key figures for a high-profile clash neither can really afford to lose.
Both teams are looking to trim the gap to first-placed Manchester City, who beat Burnley 3-0 the previous day to move five points clear at the top of the Premier League.
Spurs are eight points off Pep Guardiola's side with Liverpool a huge 12 behind, defeat to Spurs here perhaps ruling them out of the title race already after just nine games.
Tottenham are also looking to end a dreadful run of form against Liverpool, having failed to beat them once in nine league meetings since November 2012 - losing six of those encounters.
Confirmed starting line-ups
Tottenham: Lloris, Trippier, Alderweireld, Sánchez, Vertonghen, Aurier, Winks, Alli, Eriksen, Son, Kane.
Bench: Vorm, Rose, Davies, Dier, Sissoko, N'Koudou, Llorente.
Liverpool: Mignolet, Gomez, Matip, Lovren, Moreno, Henderson, Milner, Can, Salah, Coutinho, Firmino.
Bench: Karius, Alexander-Arnold, Klavan, Grujić, Oxlade-Chamberlain, Solanke, Sturridge.