Hull left it late to book their place in the play-offs of Europe's second-tier competition in their first ever continental campaign.
An 80th-minute Sone Aluko goal was required to give Hull a 2-1 aggregate win over Trencin of Slovakia in the third qualifying round, and they now meet a Lokeren side who have won three of their last four matches.
The Yorkshire outfit opened their Premier League season with a 1-0 win at QPR on Saturday but Bruce had to leave out several of his seasoned campaigners.
And the former Birmingham City and Wigan Athletic manager is keen to use his depth against the Belgian outfit.
Bruce told Hull's official website: "Lokeren are a very, very good side from what I've seen of them.
"And as we know, Belgium is producing some very good players. It will be a difficult game for us.
"As I've said, I'll be changing my team around and giving the players who got us into Europe, the chance to play in Europe.
"I think working it that way is what gives us the spirit that we're playing with. They're all going to get their chance.
"I had to leave people off the bench at QPR on Saturday. George Boyd in particular, who have [has] done wonders for me."
Lokeren sit sixth in the Belgian top flight and will be buoyed by a 2-0 win over Lierse on Saturday.
Their best result in European competition was a quarter-final appearance in the 1980-81 UEFA Cup.
Lokeren were unlucky in the 2012-13 season, as Viktoria Plzen knocked them out in the play-off stage.
After winning the first leg 2-1, Lokeren lost 1-0 in the Czech Republic to bow out of the competition on away goals.
Robert Snodgrass (knee) will miss out for Hull while defenders Alex Bruce and Liam Rosenior are doubtful with back injuries.