Tom Huddlestone returns to White Hart Lane for the first time since moving to the KC Stadium in the summer, while his former club continue to fly high in the Premier League.
The midfielder ended an eight-year stay with Spurs to join the Tigers on a permanent deal in August and has impressed during his new side's strong start to the season.
Fellow midfielder Jake Livermore also made the move from London to the KC Stadium on a season-long loan but is not eligible to face his parent club.
Tottenham's Gylfi Sigurdsson is wary of the threat provided by his eligible former colleague, however, telling his club's official website: "Tom is a fantastic player, as we all know. I saw at first hand last season just how good he can be. His passing and vision is unbelievable and, if we allow him too much time, he will find his targets and cause us damage.
"He and Jake have done really well for Hull and I'm sure their performances are one of the reasons why they have made a decent start to the campaign."
Although Hull sits ninth in the Premier League table with an encouraging tally of 11 points from nine games, the club has been beaten in three out of four away outings, the exception a 3-2 win at Newcastle.
Tottenham has only mustered four goals in as many home matches but sits three points behind Premier League leader Arsenal in fifth.
Andre Villas-Boas made seven changes for his side's Europa League meeting with Sheriff on Thursday - which Spurs won 2-0 through goals from Jan Vertonghen and Jermain Defoe - and can be expected to shuffle his pack again.
Roberto Soldado, Paulinho and Andros Townsend are among those likely to return to the home starting lineup but Hull boss Bruce does not have the luxury of being able to rotate his squad.
Indeed, with several players – including Livermore, Allan McGregor [thigh] and Danny Graham [knee] – unavailable, Bruce claims that he could struggle to name a full allocation of substitutes.
The teams have only met in the top flight on four occasions and Tottenham failed to score in each of the previous meetings at White Hart Lane, in 2008 and 2010.