Seven days after defeating second-placed Saracens 12-3 at Sixways, head coach Richard Hill takes his Warriors to the reigning English champions.
And while Hill knows The Stoop will be a difficult arena in which to produce more heroics, he insists they are targeting a second prized scalp.
"We're playing the two top teams in the Aviva Premiership in consecutive weeks and that is a big test," Hill said.
"We faced a team in Saracens who had only lost one game all season. Now we face a team in Quins who have only lost one game at home, and that was against Saracens
"It's tough for teams to go down to Harlequins and get a result.
"You have to make sure you take your three points when they're on offer and that's what we'll look to do.
"We'll have to go in with very specific tactics and Quins will be missing some of their key players.
"But they've got strength in depth; you don't win a Premiership title with 15 players so we know the size of the challenge."
Winger David Lemi returns for Worcester after completing international duty for Samoa, while Euan Murray is set to make his club debut from the bench.
Harlequins' England contingent may be in action the following day against New Zealand, but the club also welcomes back their Samoan contingent.
Tighthead James Johnston and blindside flanker Maurie Fa'asavalu start, while Seb Stegmann replaces the injured Ugo Monye.
Sale's new director of rugby John Mitchell oversees his first game in charge against Northampton at the Salford City Stadium on Friday night.
The Sharks are five points adrift at the foot of the Premiership and Northampton boss Jim Mallinder expects them to be fired up against his title hopefuls.
"Sale have been getting some disappointing results this season and we're expecting them to be very motivated for this game, especially with the return of John Mitchell to the club," he said.
"They have talented players who will no doubt be looking to prove a point.
"This season the Aviva Premiership is more competitive than ever and every point matters.
"We have had two wins in the past two weeks and now we want to build on that tomorrow."
Saints' England full-back Ben Foden returns from an ankle injury while Mark Sorenson comes in for lock Courtney Lawes, who is on the bench against New Zealand.
Sale are strengthened by the availability of Scotland lock Richie Gray while Cameron Shepherd is restored at full-back.
The pick of the weekend's action is at the Kassam Stadium on Saturday when London Welsh and London Irish clash in a potentially critical relegation encounter.
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