The 59-year-old, who left Montpellier at the end of the season after leading them to the Ligue 1 title the previous year, takes over from Rudi Garcia following his move to Roma.
A statement on the Lille website said Girard was "a natural choice" and the "ideal man" for club president Michel Seydoux and the board.
No details about the contract were given but Seydoux said: "Lille have had only two talented and loyal coaches since I took office in 2002 (Claude Puel and Garcia).
"We have appointed Rene Girard today to ensure the future of Lille has the same loyalty and success.
"I knew the coach and his record of success. I found a man of great quality, passion, spirit and hard work. For Lille and the best interests of our club, I am proud and happy to see Rene join."
Girard, a former France international midfielder, spent four years in charge of Montpellier, leading them to a surprise title triumph last spring.
This season they could finish only ninth, though, and with his contract up at the end of the campaign, Girard agreed to move on.
Girard, who has also coached the France Under-21 side, takes over a team which missed out on European qualification by a point, finishing in sixth place.
They were champions in 2011, though, also winning the Coupe de France in the same year.