Ashton scored the first of Wigan's four tries
Wigan: (12) 25
Tries: Ashton, Richards, Calderwood, O'Loughlin
Goals: Richards 4
Drop goals: Barrett
Harlequins: (0) 6
Wigan beat 12-man Harlequins to reach the semi-finals of the Challenge Cup.
Wigan took an early lead through Chris Ashton before Pat Richards, who had already kicked two goals, won the race to a kick ahead.
Quins, who had Jon Wells sent off for a high tackle after 54 minutes, hit back soon after the break through Stephen Bannister's converted try.
But further tries from Mark Calderwood and Sean O'Loughlin helped Wigan into the last four.
Ashton's opener came when he got on the end of an O'Loughlin break down the right wing.
The Warriors were checked when prop Iafeta Paleaaesina had to go off after suffering what looked to be a knee injury shortly after.
But they extended their lead when Richards won the race to a clever kick from O'Loughlin.
Bannister's try early in the second half briefly gave Quins hope, but Calderwood's try and Wells' dismissal, for a high shot on youngster Darrell Goulding, put Wigan in total control.
Trent Barrett popped over a late drop-goal before O'Loughlin's last-minute try wrapped things up.
Wigan, who were the lords of Wembley for the best part of 10 years until the 1990s, are now within a game of the first Challenge Cup final back at the rebuilt stadium.
Wigan coach Brian Noble:
"It was the right response. We were really clinical around the ruck area that we weren't last week.
"I was pleased with the way we responded. It was tough tonight. It wasn't flash or flamboyant, but sometimes you have to grind it out.
"We've matched our counterparts, who are very big and tough themselves."
Harlequins coach Brian McDermott:
"It was a very brave performance - and it's not the first time we've done that this season.
"There was some tough performances across the board from numbers 1 to 17. Everybody stepped up - I'm very proud.
"It was tough, 12-6 looks a hell of a lot better - and was probably a truer reflection of the game."
Wigan: Ashton, Calderwood, Bailey, Vaealiki, Richards, Barrett, Leuluai, Fielden, Higham, Paleaaesina, Hock, Fletcher,
Replacements: Prescott, Hansen, Goulding, Mcllorum.
Harlequins: Melling, Wells, Sykes, T Smith, A Smith, Orr, McLinden, Temata, Randall, Mills, Gafa, Hopkins, Paul
Replacements: Rinaldi, McCarthy-Scarsbrook, Worrincy, Bannister.
Referee: Ben Thaler (Wakefield)