Harvey Elliott scored his first goal in the Champions League in more than two years to secure a seventh consecutive win in the competition. However, a late goal from Barcelona in Lisbon denied them the guarantee of finishing at the top of their group.
The 2-1 win seemed to be enough to secure the top spot with a game left, but Barcelona's last-minute victory over Benfica means that the race for first place will go down to the wire.
Mohamed Salah scored his 50th European goal, but it was the 21-year-old substitute Elliott who netted the crucial goal after Liverpool's defense was breached for the first time in almost 10 hours in the tournament.
Liverpool have now secured a spot in the last-16, but coach Arne Slot would have preferred to face PSV Eindhoven with the top spot secured to have the option of resting players.
The dismissal of Aissa Mandi in the 59th minute should have eased Liverpool's evening, but Lille managed to score their only shot on target through Jonathan David shortly after.
Elliott's goal from a corner ensured Liverpool's victory without needing any last-minute heroics, unlike their previous match against Brentford.
Liverpool's performance was professional and effective, with moments of brilliance against a brave opponent in Lille who arrived on a 21-game unbeaten streak.
Salah opened the scoring in the first half after a precise pass from Curtis Jones, setting a new club record for minutes without conceding a goal in European competition.
Liverpool's defense, with some changes in the backline, held firm for most of the match, with Elliott sealing the victory with a well-taken strike.
Liverpool will now aim to maintain their 100% record as they travel to Eindhoven in pursuit of setting a new club record for successive European wins.