Defending champions Marseille cut the lead at the top to three points with two games to play but Lille's goal difference is seven better than their rivals if they finish on the same number of points.
The capitulation, the latest during Marseille's run-in, comes despite their vast experience compared to Lille.
A home victory on Wednesday will secure a first championship since 1954 for this term's surprise packages Lille, who won the French Cup on Saturday by beating Paris St Germain.
The northerners, nicknamed the Mastiffs, are now on the brink of a double which fans would not have even dreamed about at the start of the season.
Fifth-placed Stade Rennes confirmed their place in the Europa League with a 2-1 win at St Etienne, whose European hopes now look improbabley.
Lens will join already relegated Arles-Avignon in the second division next term with the final relegation place still to be determined with two rounds of matches left to play.
Second-placed Olympique Marseille visit FC Lorient later hoping to put pressure on leaders Lille, who won the French Cup on Saturday.