Hull's two-year unbeaten run in the Ladbrokes Challenge Cup came to an end as St Helens held off a late fightback to book a semi-final tie against Catalans Dragons.
Justin Holbrook's Saints side looked like they were cruising into the August 5 double header in Bolton after building up a commanding 23-18 lead after the visitors lost Danny Houghton, Danny Washbrook and Masi Matongo to yellow cards.
But efforts from Scott Taylor and Hakim Miloudi dragged the Airlie Birds back in the contest and within touching distance of Saints at 25-22 - but the home side held on.
It was a brave and gutsy display from Lee Radford's men - but not good enough to topple the Super League leaders.
Their challenge was undone when they had closed to within five points of the hosts but saw Matongo sent from the field by referee Ben Thaler for a late shot on Jonny Lomax. The resulting Danny Richardson penalty gave Saints the breathing space to book their place at the Macron Stadium.
Before the brandishing of cards in a frenetic first half, Zeb Taia had sent in Mark Percival on the left edge after quick hands and following a shocking restart from Bureta Faraimo Saints were in again as Lomax's cut-out pass was finished off in style by Regan Grace.
However, Hull hit back in determined fashion with two tries in the space of three minutes. The first was a typical stepping solo score from Australian talisman Albert Kelly and then, following a Saints' obstruction on Miloudi, Chris Green barged over from close range.
After the early Saints surge the momentum was shifting in the Airlie Birds favour but a high shot and some extra treatment from Houghton on St Helens pivot Richardson saw the Hull leader yellow carded.
Things went from bad to worse for the visitors as on the very next play as Washbrook blatantly struck Saints' Louis McCarthy-Scarsbrook while the prop was on the ground.
Those two flashpoints gifted Saints a two-man advantage in warm conditions and they made it pay with scores from Grace and Percival.
The first was put on a plate by Richardson's high bomb to the corner that Hull failed to deal with. Taia tapped it to his winger Grace, who finished off unopposed.
Then up stepped Percival as Saints piled on the pressure on the visitors' tired defence.
Richardson kicked a one-pointer with only seconds remaining of the half to give Saints a hefty advantage.
Hull's grip on the cup looked like it was slipping further when Taia touched down - but his effort was chalked off by the video official.
The visitors lost Houghton after the collision with Percival but they were undeterred and Taylor put them back in the game when he charged over.
Matongo's late shot on Lomax and the resulting yellow card was just the tonic Saints needed and Richardson's penalty inched them closer to a place in the last four.
The mood changed when Miloudi collected Kelly's kick to put Hull back in it with 10 minutes remaining - but it was not enough as Saints kept them out.
Holbrook said: "I'm relieved to have won that game. You can see today how they (Hull) won it the last two years. They kept coming and coming at us.
"I thought we were ready to control the game but never really had it. I have to give Hull a massive wrap and they really stuck it to us.
"The period when they had two in the bin probably won it for us. But it did unsettle us too.
"It unsettled them even more and they did it tough but we thought we had to win it in that little stint but it was important to get points and the tries we did.
"We tried to put them away but couldn't and credit to Hull for that."
The victory helped the Super League leaders set up a semi-final with Catalans Dragons on August 5.
Holbrook added: "We were just okay. I'm still happy that we worked hard to get the result but we weren't brilliant across the board.
"I didn't feel too threatened towards the end as we were at their end of the field but we've done enough to get the win. It's a good learning curve for us.
"Catalans is a long way away. We are ready to go and play now but that game is still a way off. They are improving but there's a fair bit of rugby league to play between now and then."
Hull coach Lee Radford could not fault his side for their effort.
He said: "I'm disappointed we got beat but unbelievably proud of the team. The lads had nothing left at the end and they were running on fumes. As a coach sometimes all you can ask for is that effort and I got that today.
"The commitment they have shown is great and they kept showing up for each other time and time again. We matched them in every department. We just kept going at them and never let down. There was certainly no lack of effort."
Hull had three men yellow carded by Ben Thaler but Radford remained tight-lipped about those decisions.
He added: "It's irrelevant - we get them we get them, we don't we don't. I can't control (the decisions) or have any influence on that.
"But I think there was one and possibly two penalties against us for our back chat. I can have an impact on that but I can't have influence on the ones I can't control. The other ones you have to kop them."