Henrik Larsson sent Manchester United into the Champions League last eight in his final game at Old Trafford.
Larsson scored his third goal for United against Lille
United had two good chances in the first half but Wayne Rooney's shot was blocked and John O'Shea hit the bar.
Lille grew in confidence but failed to capitalise as Jean Makoun wasted a header from six yards and Peter Odemwingie's header rattled the post.
Larsson sealed victory in the 72nd minute when he headed home Cristiano Ronaldo's cross from the left.
It was the 35-year-old's first Champions League goal for United and will be his last as he returns to Swedish club Helsingborg on 12 March.
Larsson left the field three minutes after scoring and paused at the edge of the pitch to salute the crowd, having sealed United's passage into the quarter-finals.
United's progress looked far from assured in a tentative start to the match and, if anything, Lille had the edge in the opening stages.
The Old Trafford crowd did their best to rouse United but they had to wait 15 minutes for the home side to hit their stride and conjure two excellent chances in quick succession.
Scholes, playing his 100th European match, sailed the ball in to a waiting Rooney in the box but his right-footed volley was blocked by Mathieu Chalme.
Michael Carrick took the resulting corner and O'Shea rose for the ball only to see his header clatter the bar while Lille keeper Tony Sylva was all at sea.
A jittery Lille defence cleared their lines and soon afterwards created their best chance to peg back United.
Ludovic Obraniak delivered a pinpoint free-kick to Makoun and he should have done better from six yards, but instead opted to tamely head to Edwin Van der Sar.
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United's frustration grew as Lille began to work their way back into the game.
Rooney found himself forced back to help out in defence far too often while at the other end Ronaldo was booked for diving in the box, although there was some contact from Chalme.
On the stroke of half-time Odemwingie fired another warning to United, just failing to get on the end of Chalme's cross, and Sir Alex Ferguson trudged off pensively.
Keita (left) worked hard for Lille Silvestre suffered a late injury
Ferguson's worries continued after the break as Lille ventured forward.
Kader Keita twice tested Van der Sar and Odemwingie came close again when his header bounced off the post before Nemanja Vidic did likewise at the opposite end.
It was Ronaldo's injection of pace which turned the match on its head after 72 minutes.
Racing up the left wing, he fed the ball to Larsson, who was unmarked in the box, and the Swede stretched to head beyond Syla.
Three minutes later, Alan Smith came on for Larsson, who after giving United the perfect farewell gift left to huge applause.
United's triumph was marred slightly as Mikael Silvestre left the field on a stretcher with a suspected dislocated shoulder in the dying minutes of the match after falling awkardly.
Man Utd: Van der Sar, Neville, Ferdinand, Vidic, Silvestre, Carrick, Scholes, O'Shea, Ronaldo (Richardson 82), Rooney (Park 82), Larsson (Smith 74).
Subs Not Used: Kuszczak, Heinze, Brown, Giggs.
Booked: Ronaldo, Richardson.
Goals: Larsson 72.
Lille: Sylva, Chalme, Tavlaridis, Plestan, Tafforeau, Makoun, Dumont (Fauvergue 74), Keita, Obraniak, Michel Bastos (Debuchy 46), Odemwingie (Mirallas 74).
Subs Not Used: Malicki, Youla, Franquart, Lichtsteiner.
Booked: Makoun, Chalme, Tafforeau, Plestan.
Ref: Luis Medina Cantalejo (Sevilla).