Spurs head into the game having beaten Leicester City 2-0 in the reply of their third round tie, and will be hoping to build on a strong season so far.
Mauricio Pochettino's men are just five points off the top of the Premier League, and have lost just three league games all season in a remarkable campaign so far.
With a knockout game in the Europa League against Fiorentina to come, Spurs are right in the mix on three different fronts - and on Saturday, the attention turns to the FA Cup.
They face a trip to Essex to take on League One side Colchester United, who sit bottom of League One, and have picked up only two points from their last ten league games.
However, Kevin Keen's men did beat Charlton Athletic in the last round, and will be hoping to spring another shock at the Weston Homes Community Stadium on Saturday afternoon.
BBC pundit Mark Lawrenson doesn't believe that will be the case though, and thinks that even though Spurs will rotate their squad, they should still get the win over the League One strugglers, and advance into round five of the competition.
"Colchester are on a dreadful run in League One, and are bottom of the table without a league win since 20 October," said Lawrenson. "I would expect Tottenham to rest most of their first-choice team, but I would still expect them to win comfortably," he added.
What's your prediction for Colchester v Tottenham?