Hull's three-game losing run came to an end but the win came at a cost as the Challenge Cup finalists lost Matt Sing, Todd Byrne and Motu Tony to injury.
Hull led 14-0 at half-time thanks to tries from Ewan Dowes and Tony and they were rarely troubled by Quins.
Tries from Graeme Horne and Kirk Yeaman piled on the misery for Quins, before Chris Melling touched down for them.
Defeat ends Quins' hopes of a top six finish and a play-off spot as Hull were left to fret over their injured squad.
Four senior players Garreth Carvell, Adam Dykes, Richard Horne and Paul King are already doubtful for the Wembley showpiece against St Helens.
Byrne and Tony were injured during the match, while Matt Sing pulled out before the game with a quadriceps injury.
Quins knew that they needed two wins from their remaining two games to stand any chance of a play-off place, but Brian McDermott's side created few noteworthy chances in a typical end-of-season encounter.
Hull coach Richard Agar:
"It's fair to say we've been leaking a few points of late in the last two or three weeks.
"It was vital that in this penultimate game before the final we had a better attitude.
"We kept them clean for 73 minutes and that's the most pleasing thing for us."
Harlequins coach Brian McDermott:
"I thought Hull were very good, and I thought their try line defence was very good.
"I think if Richard Agar wanted a good performance going into a Challenge Cup final against a very good team then he got it.
"I think he will sleep easier tonight knowing that his side have got a bit more bite back in their try line defence."
Hull: Tony, Briscoe, Byrne, Yeaman, Raynor, Washbrook, Lee, Cusack, Berrigan, Dowes, Manu, Tickle, Radford. Replacements: Houghton, Thackray, G. Horne, Wheeldon.
Harlequins: Wells, Sharp, Clubb, Howell, Sheriffe, Hill, Orr, Haggerty, Randall, Ward, Temata, Grayshon, Purdham. Replacements: Melling, Williams, McCarthy-Scarsbrook, Rinaldi.
Referee: T Alibert
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