Lilywhites head coach Ange Postecoglou has gone with an unchanged lineup from Thursday's 4-3 win over Manchester United in the EFL Cup quarter-finals, meaning that Spence keeps his place at left-back.
Postecoglou was full of praise for the former Middlesbrough man after his recent strong displays, and as a reward, he continues in the first XI over Destiny Udogie, who is at least back on the bench after injury.
Cristian Romero and Micky van de Ven missing out again means that Archie Gray and Radu Dragusin continue in the backline for the hosts, while Dominic Solanke leads the line against his former employers.
Timo Werner is also among the substitutes again following illness, but Postecoglou has unsurprisingly kept faith with Dejan Kulusevski and Son Heung-min either side of James Maddison.
Luis Diaz to start up front for Liverpool?
Meanwhile, Liverpool manager Arne Slot has made seven changes to the side that beat Southampton 2-1 in midweek, as only Trent Alexander-Arnold, Joe Gomez, Gakpo and Alexis Mac Allister hold their places.
Despite finding the back of the net at St Mary's, Darwin Nunez has been dropped from the Reds' starting lineup in favour of Diaz, who is expected to operate as Slot's centre-forward from the first whistle.
Diogo Jota is also forced to watch on from the bench despite his late equaliser against Fulham last weekend, while Dominik Szoboszlai gets the nod over Curtis Jones in the most advanced midfield position.
In defence, Andy Robertson comes straight back into the side after serving his suspension in the EFL Cup, meaning that Gomez shifts back across to the heart of defence alongside Virgil van Dijk.
There is also no space in the squad for Federico Chiesa, who made his long-awaited comeback from injury in the Southampton victory, allowing 17-year-old Trey Nyoni to make the visitors' bench.
Tottenham starting lineup: Forster; Porro, Dragusin, Gray, Spence; Sarr, Bissouma; Kulusevski, Maddison, Son; Solanke
Subs: Austin, Reguilon, Udogie, Dorrington, Bergvall, Olusesi, Werner, Johnson, Lankshear
Liverpool starting lineup: Alisson; Alexander-Arnold, Gomez, Van Dijk, Robertson; Gravenberch, Mac Allister; Salah, Szoboszlai, Gakpo; Diaz
Subs: Kelleher, Endo, Nunez, Jones, Elliott, Jota, Tsimikas, Quansah, Nyoni
Written by
Ben Knapton