The 59-year-old, who left the Stade de la Mosson at the end of the season, succeeds Rudi Garcia, who took over at Roma earlier this week.
"We have appointed Rene Girard today to ensure the future of Lille has the same loyalty and success," Seydoux told the club's official website.
"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 led Montpellier to the Ligue 1 title last year.