Mike Brown is released from England duty and comes back into the side at full-back alongside Ugo Monye. Monye sat out last week following an injury while playing for the England Saxons. They start in the back three along with Tom Williams.
George Lowe makes his first start in the Premiership since sustaining an injury in November. Lowe will partner Tom Casson in the centre, while Nick Evans and Danny Care continue their half-back partnership.
The front row sees Joe Marler returning from England duty, with Chris Brooker starting in a continuation of the rotation policy at hooker. The remainder of the pack is unchanged from London Irish last week.
James Johnston forms the cornerstone of the scrum, with Ollie Kohn and George Robson in the second row axis. Tom Guest, Luke Wallace and Nick Easter complete the back row.
Joe Gray, Mark Lambert and Tim Fairbrother will look to impact from the bench in the front row, with Tomas Vallejos and Will Skinner covering the back five. Karl Dickson and Rory Clegg provide cover at half back as Ross Chisholm covers the remainder of the backline.
Meanwhile, Worcester fly-half Danny Gray will make his first league start for the Warriors.
Gray starts in the number ten shirt, with Andy Goode and Joe Carlisle both unavailable for selection due to injury, as head coach Richard Hill makes just two changes to the side that narrowly lost to Sale Sharks.
Hooker Ed Shervington also comes into the starting line-up while versatile back Errie Claassens returns to the replacements bench.
"Quins have been very good all season to rightfully be top of the league. They play a fast open game with a strong pack and a ten in Nick Evans who controls the play and is very intelligent," said Hill.
"It's a tough game and we need to get out tactics right. We have got to try and stop them playing as they will have plenty of tempo right from the start.
"But the mindset that the players are in at the moment is that they don't mind who we play and where we play. We will go there and try and win the game.
"We need that mentality, even away from home, and that confidence. The players are in a good place, despite the loss to Sale Sharks. We made them work very hard for it and we will now go to Quins looking to make an impression."
Harlequins: 15 Mike Brown, 14 Tom Williams, 13 George Lowe, 12 Tom Casson, 11 Ugo Monye, 10 Nick Evans, 9 Danny Care, 8 Nick Easter, 7 Luke Wallace, 6 Tom Guest, 5 George Robson (c), 4 Ollie Kohn, 3 James Johnston, 2 Chris Brooker, 1 Joe Marler.
Replacements: 16 Joe Gray, 17 Mark Lambert, 18 Tim Fairbrother, 19 Tomas Vallejos, 20 Will Skinner, 21 Karl Dickson, 22 Rory Clegg, 23 Ross Chisholm.
Worcester Warriors: 15 Chris Pennell, 14 Marcel Garvey, 13 Alex Grove, 12 Dale Rasmussen, 11 Miles Benjamin, 10 Danny Gray, 9 Shaun Perry (c), 8 Blair Cowan, 7 Jake Abbott, 6 Sam Betty, 5 Chris Jones, 4 James Percival, 3 Tevita Taumoepeau, 2 Ed Shervington, 1 Matt Mullan.
Replacements: 16 Aleki Lutui, 17 George Porter, 18 Oliver Tomaszczyk, 19 Craig Gillies, 20 Matt Kvesic, 21 Jonny Arr, 22 Ravai Fatiaki, 23 Errie Claassens.
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