Gloucester have won their last five matches at Kingsholm and their only loss in their last five matches in all competitions was 15-23 at London Irish in the Anglo-Welsh Cup on 4 February.
Harlequins continue to set the pace atop the Aviva Premiership Rugby table following three wins in their last four games and have now headed the ladder since round three.
Quins have however lost their last three away games at Northampton, Connacht and Cardiff Blues.
Harlequins have won all three encounters with Gloucester this season and the final one of last season. Quins have not won at Kingsholm in the Premiership since 13 February 1999.
Harlequins have named a strong side with Ross Chisholm comes back into the side at full back as Tom Williams and Ugo Monye complete the back three.
Jordan Turner-Hall, released from England duty, will partner George Lowe in the centres. Karl Dickson starts at scrum-half to make his 50th appearance for the club, partnering Nick Evans at half back.
The front row sees Joe Gray start in a continuation of the rotation policy at hooker in between James Johnston and Joe Marler.
Ollie Kohn and Tomas Vallejos will partner in the second row to complete the front five.
George Robson picked up an injury in last week's victory over Worcester, so Nick Easter will captain the side from number 8. Tom Guest and Will Skinner complete the back-row.
Chris Brooker, Mark Lambert and Tim Fairbrother will look to impact from the bench in the front row, with Pete Browne and Luke Wallace covering the back five.
Danny Care and Rory Clegg provide cover at half back, with Matt Hopper covering the remainder of the backline.,
Gloucester Coach Bryan Redpath has kept faith with the majority of the side that defeated Bath last weekend.
Scotland internationals Jim Hamilton and Scott Lawson both featured prominently at the Rec last weekend, but are in Edinburgh representing their country against France The pair are replaced by Will James and Darren Dawidiuk respectively in the starting line up.
Meanwhile, centre Eliota Fuimaono-Sapolu picked up a knock in training this week and is replaced by Henry Trinder.
This will be the fourth time that these two sides have met this season and there is plenty of incentive for Gloucester, having lost the previous three encounters, a fact not lost upon Head Coach Bryan Redpath: "Saturday is round three of four massive matches for us and we have to make sure we're up for it.
There's no better challenge for us after three previous defeats against Quins.
"They're a good side and I've a lot of respect for them. And for Conor (O'Shea) as well. They're a rugby playing side too.
They're not a side that's boring to play against, they have some tricks up their sleeve.
"Every game we've improved. We've had our chances against them, they've just been far more clinical with the opportunities they've created.
"It's a real challenge but a good one, and one we should be looking forward to."
Match : Gloucester Rugby v Harlequins
Date : Saturday 25th February
Kick Off : 6pm
Live on: ESPN HD
Referee: Dave Pearson (159th Premiership game)
Jonny May; Charlie Sharples, Henry Trinder, Mike Tindall (capt), James Simpson-Daniel; Freddie Burns, Rory Lawson; Nick Wood, Darren Dawidiuk, Rupert Harden; Will James, Alex Brown; Tom Savage, Akapusi Qera, Matt Cox
Replacements: Matias Cortese, Dan Murphy, Shaun Knight, Peter Buxton, Brett Deacon, Dave Lewis, Ryan Mills, Tom Voyce
15. Ross Chisholm, 14. Tom Williams, 13. George Lowe, 12 Jordan Turner-Hall, 11. Ugo Monye, 10. Nick Evans, 9. Karl Dickson, 8. Nick Easter (C),7. Will Skinner,6. Tom Guest, 5. Tomas Vallejos, 4. Ollie Kohn, 3. James Johnston, 2. Joe Gray,1. Joe Marler,
Replacements, , 16. Chris Brooker, 17. Mark Lambert, 18. Tim Fairbrother, 19. Pete Browne, 20. Luke Wallace, 21. Danny Care, 22. Rory Clegg, 23. Matt Hopper