Steve Bruce's side slipped to seven points off an automatic promotion spot with the loss at Pride Park.
Steve Bruce's side appeared to have halted their slide by ending a five-match winless streak in the Championship with a convincing 4-0 win over Bristol City on Saturday.
However, a hugely disappointing display in the East Midlands has left the Yorkshire side with just one win from their last seven games and in danger of seeing their automatic promotion hopes die out.
Bradley Johnson's double in the first half set the tone of the evening and left the visitors with a mountain to climb, and things went from bad to worse when Moses Odubajo was sent off 10 minutes into the second half for bringing down Tom Ince.
Chris Martin netted a third six minutes from time and Craig Bryson added gloss to the scoreline to condemn Hull to their heaviest defeat of the season and leave them shattered at the final whistle.
Hull had a couple of bright spells during the game but their defending was simply not good enough for a promotion-chasing side and Bruce's side were, on occasion, architects of their own downfall.
Unsurprisingly, the final whistle was greeted largely with contempt from Tigers fans on Twitter as supporters become increasingly frustrated as their promotion charge falters.
@HullCity Sort it out City. You're throwing your hard work at start of season away. Come on - Dig deep, heads up & fight for promotion!— ...Mrs R... (@kerry_rawding) April 5, 2016
Win 4-0 then lose 4-0 three days later!! How the f**k does that happen?!! #DERHUL— Charlotte Sainty (@charlottesainty) April 5, 2016
How you can go from beating a team 4-0, and then 3 days later be on the receiving end of the same score line, is totally beyond me. #hcafc— Mark Taylor (@tigermark119) April 5, 2016
@HullCity oh dear...all talk of automatic may as well now stop...this rot needs stopping before play-offs begin - others are in form— Ferriby Follower (@FerribyFollower) April 5, 2016
If you've followed #hcafc for long enough you get use to losing. But what gets under the skin is the manner of this capitulation— stevej coe (@ReephamTiger) April 5, 2016
Players out of contract, owners want out, manager has to go, fans can't afford to go. Looking forward to next season #hcafc— Pete Catchpole (@thebigdogpj) April 5, 2016
For many, the humiliating defeat appears to be the final straw, with a significant number of fans beginning to believe that Bruce's time at the KC Stadium may be up.
I thought we were unlucky last season but after this season I now think it's down to the manager - I like Bruce but think time is up #hcafc— Andy White (@andywhite58) April 5, 2016
We might not even get playoffs at this rate. Embarrassing stuff from #hcafc we should be walking this league. Bruce at fault IMO— Will Jackson (@WilliamJ93) April 5, 2016
Some serious delusion knocking about. Bruce has horribly mismanaged city for two seasons. Too late to sack him but we're not going up #hcafc— Tom Collins (@grease34) April 5, 2016
Bye Bruce. You've ran out of ideas mate. Not for the first time #hcafc— Danny Hunt (@HuntyDJH) April 5, 2016