The northerners, who have 58 points from 29 games, played superbly throughout and won with goals by Aurelien Chedjou, Eden Hazard and Moussa Sow as they edge towards their first league crown since 1954.
Caen reduced the arrears through Youssef El-Arabi six minutes from time.
Third-placed Stade Rennes, also on 51 points, were held 0-0 at home by lowly AJ Auxerre. Monaco, third from bottom, kept their hopes of staying in the top flight alive with a 2-0 win at Arles-Avignon.
Paris Saint-Germain's hopes of playing in the Champions League next season took a knock as the capital side could only manage a 0-0 home draw against Lorient.
PSG, who have not won in their last four league games, stay fifth but trail Rennes by five points with nine matches left.
Montpellier boosted their European chances as they moved up to sixth with a 1-0 win at Toulouse thanks to a Souleymane Camara goal in the 75th minute.
At Villeneuve d'Ascq's Stadium Nord, where Lille play until their new stadium is built next year, the home side were once again in a class of their own.
They could have won by a much bigger margin but Yohan Cabaye missed a first-half penalty and Gervinho was superbly denied by Thomas Bosmel three times after the break.
Rudi Garcia's side went ahead on the half-hour when their Cameroon defender Chedjou headed home from a Cabaye corner and made it 2-0 through Hazard shortly after the hour.
The Belgian prodigy, twice voted the best prospect in Ligue 1, fired home after a bad clearance by the Caen defence.
Sow, the league's top scorer, netted his 20th goal of the season when he tapped in from a Gervinho cross 17 minutes from time to put the result beyond doubt.
"We are on the right track. If we continue like this, it will be all good," Belgian midfielder Hazard, arguably the best Ligue 1 player this season, told French TV channel Foot Plus.
"We just put the pressure on Marseille. If they don't win, we'll have increased our lead."
