Third-placed Olympique Marseille drew 0-0 at home to lowly Valenciennes while Toulouse beat Girondins Bordeaux 3-0.
Lyon have 53 points ahead of PSG on 52 while Marseille have 49 ahead of Toulouse on goal difference.
It was the second time this week that Lyon, aiming for an eighth consecutive title, had lost to Lille after going down 3-2 in the last 16 of the French Cup on Wednesday.
Lyon striker Karim Benzema, who was carrying a slight hip injury, went off after the first half while captain Juninho was also substituted in the second period.
Benzema, who was initially hurt last Sunday, is a doubt to face Barcelona on Wednesday with the teams level at 1-1 after the first leg at Stade Gerland.
VITTEK HEADER
Lille went ahead just before the hour mark when their Brazilian forward Michel Bastos crossed from the left wing and Slovakian striker Robert Vittek got in between the two central defenders to head the ball into the net.
Bastos himself scored the second goal in the 90th minute, capitalising on hesitancy in the Lyon defence to intercept the ball and chip it over the goalkeeper.
Lyon earlier had a lucky escape at the start of the second half when Lille midfielder Yohan Cabaye hit the bar.
About 78,000 spectators were present at the Stade de France -- a record attendance for a French club match.
Paris St Germain's victory at Lorient, who missed a penalty, helped to erase the memory of their humiliating defeat in the French Cup this week at the hands of third division side Rodez.
Former France forward Ludovic Giuly scored the only goal with a stunning volley from just outside the area in the 22nd minute after towering striker Guillaume Hoarau headed the ball back across the box following a free kick.
Ten minutes from time PSG keeper Mickael Landreau saved a penalty by Lorient striker Rafik Saifi.
Caen slipped closer to the relegation zone after losing 2-1 at Grenoble to stand 17th while the Riviera derby between Nice and Monaco ended in a goalless draw.
On Sunday, St Etienne play Nantes with both teams fighting to survive in the top flight.
