Liverpool face an uphill task to progress from the last 16 of the Europa League after Eden Hazard's goal gave a lively Lille side a first-leg lead.
After the hosts' bright opening, it took a superb double save from Mickael Landreau to deny Steven Gerrard and Fernando Torres and maintain parity.
Yohan Cabaye went close before Hazard's free-kick floated over a packed penalty box and into the far corner.
Torres threatened late on but was crowded out by a scrambling defence.
After tripping up away to Wigan three days earlier in the league, Benitez had claimed the match would provide his side an immediate chance to recover their stride.
But it was Rudi Garcia's side who were faster out of the traps as Cabaye exercised Jose Reina with a well-struck shot and Hazard's dangerous low ball fizzed clear across the six-yard box.
The French side held Valencia at Stadium Lille Metropole to a draw in the group stages and their crisp passing in the first 20 minutes suggested Rafael Benitez might be satisfied to repeat his previous club's result.
Some slick interplay of their own conjured Liverpool's first opening as Ryan Babel and Torres exchanged passes to slice open the defence before the Dutchman saw his shot blocked by Mickael Landreau.
The goalkeeper came to his side's rescue again after an electric burst from Torres took the ball from halfway to the edge of the box before drawing a foul from the chasing pack of defenders.
Landreau first palmed away Steven Gerrard's fierce drive before clawing out a header from Torres that seemed destined for the net.
The 19-year-old Hazard was impressive throughout and his darting run behind the Liverpool defence after the interval seemed timed to perfection, but his progress was harshly halted by the assistant referee's flag.
At the other end, Landreau was fortunate when Babel unleashed a ferocious shot straight at him before Liverpool also enjoyed an escape as Daniel Agger narrowly avoided putting the ball into his own net.
A superb long-range effort from Cabaye had Jose Reina worried as it whistled over the bar before the Spanish goalkeeper took two attempts to grasp substitute Stephane Dumont's skidding shot.
A awkward challenge from Jamie Carragher prompted penalty appeals from the hosts, but the hosts' pressure was finally rewarded when Hazard's curling set-piece cleared everyone and bounced into the bottom Reina's goal.
A last-ditch challenge from Agger did just enough to divert Pierre-Emerick Aubameyang's effort on to the post as Lille threatened to take a more comfortable advantage to Anfield on 18 March.
As time ran out Torres was afforded a brief glimpse of goal but the ball was ushered away before the striker could pull the trigger.
Team Line-ups and Substitutions
Lille: Landreau, Emerson, Beria, Lami, Balmont, Cabaye (Dumont 73), Obraniak (Toure 83), Chedjou Fongang, Mavuba, Hazard, Frau (Aubameyang 77).
Liverpool: Reina, Johnson, Agger, Insua, Carragher, Gerrard, Mascherano, Lucas, Torres, Kuyt (El Zhar 88), Babel (Riera 73).
Referee: Alan Larsen