The Lilywhites had little answer to the Tigers' front line who were far too good for them on the night and well worth their big victory.
But for Declan Rudd the margin of defeat could have been greater, the North End goalkeeper pulling off a series of saves.
PNE hit the woodwork twice, Sean Maguire'sa shot coming back off the post early doors, while substitute Josh Harrop did so later on when the contest was out of sight.
Jarrod Bowen opened the scoring in the 30th minute from close range, Josh Magennis doubling the lead from the penalty spot two minutes into the second half.
Kamil Grosicki made it 3-0 soon after, with the excellent Bowen scoring the fourth from a narrow angle 13 minutes from time.
It was North End's second defeat on the bounce after the 1-0 reverse at Derby last Saturday, and they now face leaders West Bromwich Albion at Deepdale on Monday night in front of the Sky Sports cameras.
The North End side had shown four changes, the most surprising seeing midfielder Ryan Ledson start at right-back.
He was pressed into service there with Darnell Fisher and Alan Browne both out injured. Jordan Storey replaced the injured Ben Davies, with Paul Gallagher and Billy Bodin coming into the starting XI.
Ledson had a torrid night out of position, with his switch to left-back for the second half just adding to his misery.
Preston started brightly and hit the post inside the opening five minutes, Maguire's curling right-foot shot from the edge of the box travelling across goal and hitting the far post.
The rebound was picked up by Gallagher just inside the box, his low shot deflected inches past the post by a Hull defender.
At the other end, Patrick Bauer slid across to get a touch on Grosicki's shot and take it over the bar.
Tom Barkhuizen, playing as the central striker in a 4-2-3-1 formation, brought a diving save out of Tigers goalkeeper George Long after Maguire's clever pass had found him space 20 yards out.
A teasing right-wing cross from Bodin deceived Long and had to be put out for a corner at the far post by Eric Lichaj.
Two good pieces of play by Maguire saw North End twice go close, his driving run into the box in the 28th minute almost playing in Daniel Johnson but the midfielder got ahead of the pass and the opportunity went begging.
Soon after Maguire got down the left hand side of the box and drilled over a low cross which Hull left-back Callum Elder almost turned into his own net before managing to recover to clear his lines.
Hull took the lead on the half-hour mark, helped by a touch of good fortune.
Grosicki's cross with the outside of his right foot from the left-wing clipped off Storey on its way and then hit Joe Rafferty in the six-yard box.
That touch from Rafferty took it back across Rudd and Bowen nipped in to squeeze the ball over the line by the far post.
Rudd then kept North End in the game with three saves in the run-up to the interval.
Gallagher's slack square pass in midfield saw the hosts counter through Grosicki who drove up field through the middle and hit a shot which Rudd dived to parry.
He got fingertips to a shot from Josh Bowler to push it over the bar, then did really well to smother a shot from Grosicki who had tried to slip the ball under him.
All of Rudd's good work in keeping the deficit down to a single goal at the interval was undone by two Hull goals in the space of three minutes at the start of the second half.
Ledson was moved to left-back at half-time, swapping with Rafferty, and in his new position he conceded the penalty from which Hull made it 2-0 in the 48th minute.
His trip on Josh Bowler saw referee Jon Moss point to the spot, Magennis putting it away despite the best efforts of Rudd who got his gloves to it.
The home side got their third goal in the 51st minute, Magennis clipping a pass down the right hand side of the box to play in Bowen, his pass inside presenting Grosicki with the easiest of finishes from close range.
Rudd was called into action again, getting down low to parry a Grosicki free-kick, the rebound scooped over the top by Jackson Irvine.
Ledson's substitution in the 58th minute put him out of his misery, Harrop replacing him. Johnson dropped back to take Ledson's left-back slot.
North End went close twice as they looked to give the scoreline a more respectable look.
Patrick Bauer fired a shot into the side-netting after meeting a Gallagher free-kick, some of the PNE fans in the stand behind the goal momentarily thinking it had gone in.
Then in the 70th minute, David Nugent got away down the right channel and sent over a low cross which fellow substitute Harrop shot against the post from 12 yards.
However, the misery continued at the other end as Hull made it 4-0 in the 77th minute.
Bowen got the space to take the ball down the right hand side of the box, cut inside on to his left side and squeeze a shot between Rudd and his near post - the one stain on the keeper's evening.
Hull: Long, Lichaj, Burke, de Wijs, Elder, Batty, Irvine, Bowler (Honeyman 71), Bowen, Grosicki (Lewis-Potter 78), Magennis (Eaves 78). Subs (not used): Tafazolli, Stewart, Pennington, Ingram.
PNE: Rudd, Ledson (Harrop 58), Bauer, Storey, Rafferty, Pearson, Gallagher, Bodin (Nugent 67), Johnson, Maguire (Potts 81), Barkhuizen. Subs (not used): Bayliss, Stockley, Huntington, Hudson.
Referee: Jon Moss (West Yorkshire)