The French outfit are one point clear of AC Milan at the top of Group H, whereas Sparta are looking to keep their own European ambitions alive as they sit one point behind Milan in third.
After an inspired performance from Arsenal-linked Yusuf Yazici saw Lille take all three points at San Siro, Les Dogues' second meeting with Milan last week was a much more low-key affair by comparison.
Samu Castillejo struck first for the in-form Rossoneri, but Jonathan Bamba ensured that Lille's unbeaten start to the 2020-21 Europa League was preserved as both teams walked away with a point apiece on matchday four.
Christophe Galtier's men cannot afford to head into their clash with Sparta thinking that they have already secured a spot in the next round, though, as Milan will certainly be expected to triumph against basement side Celtic on Thursday evening.
However, with 10 goals scored and zero defeats to their name in Group H, a spot in the round of 32 will be guaranteed for Lille should they take the spoils against Sparta, whom they thrashed 4-1 in October courtesy of another Yazici hat-trick.
Les Dogues' preparations for this European showdown were far from ideal, however, as Saint-Etienne ended a seven-game losing run by holding Galtier's side to a 1-1 draw at the weekend, with Lille now boasting just two wins from their last eight in all competitions.
Sparta will be equally desperate to come up trumps in their visit to the Stade Pierre-Mauroy, with the Czech giants still in with a chance of pipping Lille or Milan to one of the top two spots in the group.
Vaclav Kotal's men suffered two crushing defeats to the French and Italian powerhouses early on, but Sparta have since recorded a pair of 4-1 victories over an out-of-sorts Celtic side to put themselves in contention for a knockout berth.
A shock victory on French turf would see Sparta leapfrog Lille before the final matchday in the group, and even a draw would keep their chances of a spot in the next round alive, but the Czech giants will be eliminated if they suffer defeat and Milan prevail against Celtic.
Kotal's men will be heading into this fixture with a renewed sense of optimism after they picked up a vital victory over Teplice in the Fortuna Liga, with Lukas Julis notching up his 11th goal of the season in a 1-0 win, but Sparta must also keep this weekend's derby with Slavia Prague in mind.
Lille Europa League form: WDWD
Lille form (all competitions): DWLWDD
Sparta Prague Europa League form: LLWW
Sparta Prague form (all competitions): LWLLWW
Portuguese midfielder Renato Sanches is still trying to shake off a muscular problem and is unlikely to come back in time for the visit of Sparta, but Galtier could make a change in the engine room anyways as Xeka is in line to replace Boubakary Soumare.
Six-goal Yazici is sure to come back into the starting lineup for Thursday's game, while Bamba and Jonathan David should also return to Galtier's first XI after only making the bench against Saint-Etienne.
Sparta defender Ondrej Celustka returned from injury to complete the full 90 minutes against Teplice, but the 31-year-old may make way for David Lischka here, with David Hancko's involvement uncertain.
Lille possible starting lineup:
Maignan; Djalo, Botman, Fonte, Reinildo; Ikone, Andre, Xeka, Bamba; David, Yazici
Sparta Prague possible starting lineup:
Nita; Lischka, Plechaty, Hancko; Vindheim, Krejci, Dockal, Travnik, Hanousek; Julis, Plavsic
We say: Lille 2-1 Sparta Prague
Lille's results have been somewhat underwhelming in the past few weeks, but Galtier can afford to breathe easy should Les Dogues safely secure their passage into the next stage this week. The hosts have already trounced Sparta on their own turf and will welcome some big hitters back to their starting lineup, so we expect Lille to book their place in the round of 32 with a narrow win here.