Full-backs Thomas Meunier and Romain Perraud netted either side of the break before Matias Fernandez-Pardo and Olivier Giroud wrapped up the victory to send Bruno Genesio’s side back above Marseille into the final Champions League qualification spot.
Lille have 53 points, one more than Habib Beye’s Marseille in the battle for a direct spot in the league phase of the next edition of Europe’s premier club competition.
“We did what we had to,” Lille coach Genesio said.
“We knew this match was important, but there are still five more to go, and we’ll need to keep performing as we have been doing lately.”
Right-back Meunier’s deflected effort finished off a slick team move to send Lille in front on 23 minutes.
Lille celebrated the goal by flocking to their coach, who recently lost his father.
Genesio said he was “deeply moved” by the unexpected gesture, adding: “It shows the spirit of this team, and it is also thanks to that that we are achieving the results we are.”
The hosts, safely ensconced in 10th spot in the table, seemed to already have one eye on their upcoming French Cup semi-final with surprise Ligue 1 title challengers Lens and rarely threatened, barring one frantic corner at the quarter hour which saw the ball rebound off the Lille goal.
The encounter was ultimately decided inside the opening five minutes of the second period.
Nabil Bentaleb threaded an excellent through-ball for Fernandez-Pardo to run onto before he was hauled down by a retreating Mark McKenzie, who promptly received his marching orders.
From the resulting set-piece, left-back Perraud drilled a fizzing low shot from a central position 25 yards out from goal, which flew past Toulouse goalkeeper Guillaume Restes.
Belgian forward Fernandez-Pardo then made it three as the 21-year-old turned on captain Benjamin Andre’s pass and stroked home right-footed on 55 minutes.
Giroud converted from the spot two minutes from time to notch his seventh goal of the league campaign.
Lyon, fifth, remained in contention for direct Champions League qualification with a 2-0 home win over mid-table Lorient later on Sunday.
The breakthrough came for Paulo Fonseca’s side four minutes into the second period as Real Madrid loanee Endrick came off the bench at the interval to supply a pinpoint cross onto the head of Roman Yaremchuk.
Corentin Tolisso, also introduced at half-time by Portuguese coach Fonseca, ensured the hosts would claim all three points in the 56th minute when he nodded into the empty goal after Yvon Mvogo had denied Endrick one-on-one.
Nice drew 1-1 with Le Havre in a battle of two sides seeking to put more distance between themselves and the relegation play-off spot.
Ally Samatta sent Le Havre ahead on 41 minutes before Ali Abdi grabbed a vital leveller for the hosts just shy of the hour.
Nice trail their opponents by one point but remain four clear of 16th-placed Auxerre.