Spurs face Manchester United at Wembley, with the competition having taken on an added weight for both sides given their respective seasons.
With a summer exit looking ever more likely, Alderweireld has been left out ahead of a big game once more, with the Argentine taking much the same approach as he did with Kyle Walker last season.
Michel Vorm, Spurs’ traditional Cup ‘keeper, replaces Hugo Lloris in goal while Heung-min Son, who has contributed more goals and assists than any other player in the FA Cup over the past three seasons, gets the nod ahead of Erik Lamela.
For Jose Mourinho, both Marcus Rashford and Anthony Martial have been named on the bench, while former Arsenal man Alexis Sanchez starts.
Today also marks a year to the day former Spurs coach Ugo Ehiogu passed away. Tottenham pay tribute with two pages in the programme and a memorial video at Wembley ahead of kick-off.
Starting line-ups in full...
Manchester United XI: De Gea; Valencia, Jones, Smalling, Yoing; Matic, Herrera, Pogba; Lingard, Lukaku, Alexis Sanchez
Substitutes: Pereira, Darmian, Lindelof, Fellaini, Mata, Martial, Rashford
Tottenham XI: Vorm, Trippier, Sanchez, Vertonghen, Davies, Dier, Dembele, Eriksen, Dele, Son, Kane.
Substitutes: Lloris, Aurier, Alderweireld, Wanyama, Sissoko, Lamela, Lucas