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A solitary goal from Hans Vanakan on 59 minutes left Hull's European campaign hanging in the balance ahead of next Thursday's return leg at the KC Stadium.
It was the visitors who started the better of both sides, and Bruce's charges should have moved ahead after seven minutes when Yannick Sagbo scuffed wide of the mark from inside the box.
The hosts slowly grew into the encounter but it took the best part of half an hour for them to threaten Allan McGregor's goal.
Lokeren maintained that momentum after the break and it was De Pauw again who threatened, forcing McGregor to palm away his 25-yard thump.
The Scottish goalkeeper went from hero to villain on the hour mark, though, as McGregor passed straight to Vanakan, who then rounded him before tapping into an empty net.
It would prove as close as the Premier League side would come to bagging a timely away goal and Lokeren held out to draw first blood in the tie.