And while Danaher will reach the personal milestone, at the other end of the scale Anthony Watson will start a Premiership match for the first time.
Both players starred in the 69-26 romp against Mont-de-Marsan in the Amlin Challenge Cup last time out - with director of rugby Brian Smith keeping faith in the same line-up.
There are three changes on the bench, though, with Cai Griffiths, Alex Gray and Darren Allinson coming in.
Harlequins have made three changes for the trip to the Madejski Stadium.
The table-toppers, who recorded back-to-back wins in the Heineken Cup, welcome back Ugo Monye and Tom Casson to the back division, while Tom Guest comes into the back row.
Casson is handed his first start of the season as Jordan Turner-Hall is given the week off to rest an on-going knee problem.
With Nick Evans still sidelined, Ben Botica retains the No 10 jersey.
London Irish: 15 Anthony Watson, 14 Topsy Ojo, 13 Jonathan Joseph, 12 Guy Armitage, 11 Sailosi Tagicakibau, 10 Ian Humphreys, 9 Tomas O'Leary, 8 Chris Hala'ufia 7 Jamie Gibson, 6 Declan Danaher (c), 5 Matt Garvey, 4 Bryn Evans, 3 Halani Aulika, 2 David Paice, 1 Max Lahiff.
Replacements: 16 Scott Lawson, 17 Cai Griffiths, 18 Leo Halavatau, 19 Kieran Low, 20 Ofisa Treviranus, 21 Alex Gray, 22 Steven Shingler, 23 Darren Allinson
Harlequins: 15 Mike Brown, 14 Tom Williams, 13 Matt Hopper, 12 Tom Casson, 11 Ugo Monye, 10 Ben Botica, 9 Danny Care, 1 Joe Marler, 2 Rob Buchanan, 3 James Johnston, 4 Olly Kohn, 5 George Robson, 6 Tom Guest, 7 Chris Robshaw (capt), 8 Nick Easter.
Replacements: 16 Dave Ward, 17 Mark Lambert, 18 Will Collier, 19 Charlie Matthews, 20 Maurie Fa'asavalu, 21 Karl Dickson, 22 Rory Clegg, 23Seb Stegmann
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