Bob Casey is the only change to the side that saw off Worcester and he has been named captain for his 235th and final appearance.
England international Delon Armitage will also be playing his last match for the Exiles before departing for Toulon, while Paul Hodgson and Kieran Roche, who are also leaving, are named amongst the replacements.
It is not just players who will be signing off, either. It will also be the final match for attack coach Mike Catt after eight seasons with the club.
"Tomorrow (Saturday) gives us the opportunity to continue the momentum we gained from the win over Worcester to take into our pre-season," said head coach Toby Booth.
"It will also mark the end of an era to players who have been great servants to our club. I am sure the supporters will turn up in their numbers to say goodbye."
Meanwhile, Gloucester head to the capital with nothing to play for but pride following a series of disappointing results that have dropped them down to eighth in the Aviva Premiership table.
Scotland international Jim Hamilton will captain the Cherry and Whites, who remain under the leadership of Carl Hogg following Bryan Redpath's departure.
Tom Voyce is named at full-back with Jonny May partnering Mike Tindall in midfield as Tim Molenaar is unwell. Ollie Phillips gets a start on the wing.
Darren Dawidiuk is preferred to Scott Lawson at hooker while Tom Savage comes in for Peter Buxton on the blindside flank. Alasdair Strokosch moves across from number eight to openside.
"It's been a difficult end to the season but we intend to go down to London Irish and challenge ourselves. It's a difficult fixture but one we're looking forward to," Hogg said.
"Training this week has been very buoyant, it's been very upbeat. It's our last game and the group have been enthused this week.
"As a professional, you take pride in going out and performing to the best of your ability and the enthusiasm and effort this week has been excellent. Hopefully, that will translate to the pitch on Saturday."
London Irish: 15 Tom Homer, 14 Delon Armitage, 13 Jonathan Joseph, 12 Joe Ansbro, 11 Sailosi Tagicakibau, 10 Steve Shingler, 9 Darren Allinson, 8 Ofisa Treviranus 7 David Sisi, 6 Jamie Gibson, 5 Bob Casey (Captain), 4 Bryn Evans, 3 Leo Halavatau, 2 David Paice, 1 Max Lahiff.
Replacements: 16 James Buckland, 17 Paulica Ion, 18 Faan Rautenbach, 19 Matt Garvey, 20 Kieran Roche, 21 Marland Yarde, 22 Adrian Jarvis, 23 Paul Hodgson.
Gloucester: 15 Tom Voyce, 14 Charlie Sharples, 13 Jonny May, 12 Mike Tindall, 11 Ollie Phillips, 10 Freddie Burns, 9 Dave Lewis, 8 Matt Cox, 7 Alasdair Strokosch, 6 Tom Savage, 5 Alex Brown, 4 Jim Hamilton (capt), 3 Rupert Harden, 2 Darren Dawidiuk, 1 Dan Murphy.
Replacements: 16 Scott Lawson, 17 Yann Thomas, 18 Shaun Knight, 19 Peter Buxton, 20 Akapusi Qera, 21 Dan Robson, 22 Tim Taylor, 23 Ian Clark.
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