Dupuy, 28, moved to Leicester in the summer of 2008 after unsuccessfully competing for a place in the Biarritz team with Dimitri Yachvili. He became the first choice scrumhalf, condemning Harry Ellis and Ben Youngs to a place on the bench.
He kicked 12 points in his test debut when France upset the current world champions New Zealand 27-22 in Dunedin in 2009 and played in France's next five tests.
This year he was included in the France squad after Yachvili withdrew through injury and came on as substitute for a few minutes in the 23-17 win over Scotland.
He replaces Morgan Parra for the match with Lionel Beauxis, taking over from Francois Trinh-Duc at flyhalf.
"It's such a pleasure to start this match, especially against England. I longed for it. The pressure is going to weigh but I am not that stressed", Dupuy told a news conference.
"I know the English well, I'm really pleased playing against them. I would be all the more pleased meeting Leicester players after our victory."
On his return to France where he joined Stade Francais, Dupuy was given a 23-week ban in 2010 for eye-gouging Ulster's Stephen Ferris in an Heineken Cup match.
"It's over. I made a gesture I should not have done and I was punished for it, period. I try to have as much pleasure as I can and enjoy. What happened helps me put it all in perspective", he said.
"It's like ages (ago) to me. I am more mature, I spent three years without France. But playing for France has always been a goal."
