The Sharks will end their nine-year stay at the venue in Stockport before moving to Barton to groundshare with rugby league side Salford City Reds.
However, the hosts cannot afford to let sentiment get in the way of the job in hand; they need a solitary point from their final fixture to secure a place in next season's Heineken Cup.
They will have two players making their senior debuts this weekend - Tommy Bell, who has been at Leeds Carnegie through the season, and Will Bordill.
Bordill has appeared for Preston Grasshoppers along with flanker Billy Emerson, who is named on the bench and is also lined up for a debut.
Andrew Sheridan misses the game through injury, denying him a final outing for Sale before he heads to the Top 14. Northampton-bound Luther Burrell does, however, start in the centres.
"There is plenty to play for on Saturday. We'll have a youthful team to try and combat the way that Harlequins play," said Sharks' chief executive Steve Diamond.
"There should be a large crowd to see us say farewell to Edgeley Park and we are all looking forward to it."
Quins, meanwhile, have plenty to play for as well. A win for the capital club on the road will seal first place and a semi-final at the Twickenham Stoop on May 12.
The visitors are without Ugo Monye, who is undergoing further treatment following his injury against Leicester and will be reassessed early next week.
Joe Gray returns at hooker to make his 50th appearance, and he is the only change from the pack that faced the Tigers last time out.
Captain Chris Robshaw starts to make his 100th Premiership appearance, with Maurie Fa'asavalu and Nick Easter completing the back row.
The last seven clashes between the two clubs in the Aviva Premiership have all been won by the home side, though Quins triumphed at Edgeley Park this season, in the Anglo-Welsh Cup last October.
Sale Sharks: 15 Rob Miller, 14 Tom Brady, 13 Will Addison, 12 Luther Burrell, 11 Mark Cueto, 10 Tommy Bell, 9 Scott Mathie, 8 Mark Easter, 7 David Seymour (capt), 6 Will Bordill, 5 Tom Holmes, 4 Kearnan Myall, 3 Henry Thomas, 2 Marc Jones, 1 Lee Imiolek.
Replacements: 16 Tommy Taylor, 17 Ross Harrison, 18 Joe Ward, 19 Billy Emerson, 20 Jordan Davies, 21 Will Cliff, 22 Iain Thornley, 23 Charlie Amesbury.
Harlequins: 15 Mike Brown, 14 Tom Williams, 13 George Lowe, 12 Jordan Turner-Hall, 11 Sam Smith, 10 Nick Evans, 9 Danny Care, 8 Nick Easter, 7 Chris Robshaw (capt), 6 Maurie Fa'asavalu, 5 George Robson, 4 Olly Kohn, 3 James Johnston, 2 Joe Gray, 1 Joe Marler.
Replacements: 16 Rob Buchanan, 17 Mark Lambert, 18 Will Collier, 19 Tomas Vallejos, 20 Tom Guest, 21 Karl Dickson, 22 Rory Clegg, 23 Matt Hopper.
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