Swansea City will be looking to continue their impressive record against the top sides this season and progress into the next round at Wembley.
While Tottenham's departure from the Champions League will have left them even more determined to claim the FA Cup trophy this season.
Spurs are on a good run in the Premier League, the only team unbeaten in 2018, and their win against Bournemouth at the weekend moved them up to third in the table.
Swansea have had some big results this year, beating Liverpool and Arsenal at the Liberty Stadium in 2018, and have only lost one of their last 10 fixtures.
However, neither side have had a smooth run in the competition so far. Swansea have needed a replay in all three previous rounds of the FA Cup this season, eventually passing Wolves, Notts County and Sheffield Wednesday to claim their place in the quarter finals.
And while Spurs convincingly beat AFC Wimbledon as they entered the competition in January, they too have needed replays in the last two rounds to pass Newport and Rochdale.
Swansea and Spurs have come up against each other 45 times in total, with the London side winning 28 of those clashes.
After a tight game at Wembley in September resulted in Swansea holding Spurs to a 0-0 draw, the Lilywhites ran out 2-0 winners as they traveled to Wales in January.
Kristoffer Nordfeldt vSon Heung-Min
Swansea's Swedishkeeper has kept three clean sheets so far in the competition, conceding only once in each of the other three fixtures. But the 28-year-old will be facing a challenge to keep up that good record against Tottenham's attack.
Son has been in brilliant form, scoring seven goals in his last four appearances for Spurs. His pace and skill will be a major threat for Nordfeldt in the Swansea goal.
Swansea will be without Jordan Ayew for the game on Saturday, after the forward was shown a red card within 11 minutes against Huddersfield at the weekend.
Renato Sanches could return from injury and Leon Britton is now fit for selection again after recovering from a back problem.
Wilfried Bony, Leroy Fer and Angel Rangel all remain sidelined for the Swans.
It is all but confirmed that Spurs will be without Harry Kane for the FA Cup clash this weekend, after the striker limped off with an ankle injury on Sunday.
Dele Alli and Danny Rose both also left the pitch against Bournemouth after picking up knocks, but boss Mauricio Pochettino claimed that neither problem was serious.
Eric Dier and Ben Davies are expected to return after being benched and rested respectively due to fatigue.
And Spurs center back Toby Alderweireld continues to be assessed after not fully recovering from a hamstring injury he sustained in November.
Potential Swansea Starting Lineup: Nordfeldt; Naughton, van der Hoorn, Fernandez, Mawson; Ki Sung-yueng, Carroll, Clucas, Dyer; Abraham, A Ayew
Potential Tottenham Starting Lineup: Vorm; Trippier, Sanchez, Vertonghen, Davies; Dier, Dembele; Lamela, Eriksen, Lucas; Son
This is likely to be a tight game, with both sides fighting for a place in the semifinals. Spurs will be favorites to progress but the Liberty Stadium is not an easy place to visit, and Swansea can be a very difficult team to break down.
However, with a result needed on the day Swansea will have to go for the win, which could open things up and allow Spurs to play the attacking, fast paced football they excel at.
Prediction: Swansea 0-2 Tottenham