The Exiles opened up with an impressive 43-16 victory at Bordeaux-Begles last week and Smith has named another strong team for the visit of Mont-de-Marsan in Pool One.
The visitors prop up the Top 14 but they gave Gloucester an uncomfortable evening in France last week, and Smith has resisted the temptation to give some of his star men the weekend off.
Captain Declan Danaher returns to the back row in place of Ofisa Treviranus and England Under 20-star Anthony Watson will start at full-back in place of Steven Shingler, who drops to the bench.
London Irish: 15 Anthony Watson, 14 Topsy Ojo, 13 Jonathan Joseph, 12 Guy Armitage, 11 Sailosi Tagicakibau, 10 Ian Humphreys, 9 Tomas O'Leary, 1 Max Lahiff, 2 David Paice, 3 Halani Aulika, 4 Bryn Evans, 5 Matt Garvey, 6 Declan Danaher, 7 Jamie Gibson, 8 Chris Hala'ufia.
Replacements: 16 Scott Lawson, 17 Jerry Yanuyanutawa, 18 Leo Halavatau, 19 Kieran Low, 20 Ofisa Treviranus, 21 Conor Gaston, 22 Steven Shingle, 23 Jack Moates.
Mont-de-Marsan: TBC.
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