The Italian side are the only team still without a goal in this season's league phase, leaving them trailing behind their French counterparts, who are firmly on track for a playoff place.
Match preview
After playing out a goalless draw at home to Shakhtar Donetsk on their long-awaited Champions League debut, Bologna have been unable to add more points to their tally, twice losing 2-0 in England - to Liverpool and then Aston Villa - before being beaten by Monaco last time out.
The Rossoblu's wait for a first win continued as Thilo Kehrer's late goal denied them even a home draw earlier this month, and they occupy an automatic elimination place as things stand.
Heading into the second half of the league phase, Vincenzo Italiano's side cannot afford to keep dropping points, with perhaps as many as three wins from four games now required to make the top 24 and avoid an early exit.
On Sunday, a nine-match unbeaten run in domestic football was finally ended when Bologna lost 3-0 to Lazio in Rome, with all three goals coming during the second half as legs tired due to playing for an hour with 10 men - Tommaso Pobega's senseless dismissal turned the game on its head.
Before the international break, the Emilian club had posted three successive Serie A wins, but they now sit eighth in the standings, having won just four of 16 games across all competitions.
Only one of those successes has come at the Dall'Ara, where Bologna's fans have been starved of reasons to celebrate since Italiano took the reins from Thiago Motta - they have scored a meagre four goals in seven home fixtures this season.
By contrast with their hosts, Lille have made an impressive start to their latest Champions League campaign, establishing themselves as contenders for the top-eight finish that would evade any need for a playoff to reach the knockout rounds.
After coming through qualifying, and suffering an opening defeat to Sporting Lisbon, Bruno Genesio's side memorably turned over mighty Real Madrid on home turf, before going on to defeat the defending champions' city rivals Atletico Madrid three weeks later.
Before the break, a 1-1 home draw with Juventus took Les Dogues onto seven points at the halfway stage, with star striker Jonathan David netting his fourth goal from as many games in the league phase before Dusan Vlahovic pulled Juve level from the spot.
Now set to face another Italian team, Lille come into Wednesday's contest unbeaten in 11 matches since losing in Lisbon, and David has scored 10 times during that streak.
Edon Zhegrova's first-half strike secured victory over Rennes on Sunday, keeping LOSC fourth in the Ligue 1 table - albeit they stayed 10 points adrift of relentless leaders Paris Saint-Germain, who are on course for yet another French title.
As the win against Atleti was Lille's third from their last five away games in UEFA's top club competition, they can now set off for Emilia-Romagna fully confident of extending such a fine run of form.
Bologna Champions League form:
D
L
L
L
Bologna form (all competitions):
L
W
W
L
W
L
Lille Champions League form:
W
L
L
W
W
D
Lille form (all competitions):
W
W
D
D
D
W
Team News
In addition to long-term absentees Nicolo Cambiaghi and Oussama El Azzouzi, Bologna have also been missing Swiss stars Michel Aebischer and Dan Ndoye of late, with Ndoye injuring his shin on a goalpost just before the international break.
First-choice goalkeeper Lukasz Skorupski sat out the Rossoblu's weekend loss due to illness, so Federico Ravaglia is on standby to deputise again, while Martin Erlic and Lewis Ferguson are both back in contention - the latter recently celebrated his return from an ACL injury by signing a new contract.
In the final third, captain Riccardo Orsolini had scored in four Serie A games straight before firing a blank on Sunday: four of his five goals this term have been the first of the match. He should support either Thijs Dallinga or Santiago Castro up front.
Across the first four matchdays, Lille made the most changes to their starting XI (16), so their lineup is a little more unpredictable: Lucas Chevalier, Alexsandro and Benjamin Andre are the only three players to have started every league-phase game so far.
A certain starter is Jonathan David, who netted his 31st goal for Canada in the CONCACAF Nations League quarter-finals last week, becoming his country's all-time top scorer.
Edon Zhegrova is also set to feature in the visitors' attack, having been directly involved in half of Lille's 24 shots in this season's Champions League.
Hakon Arnar Haraldsson, Ismaily and Thomas Meunier have all returned to the squad following layoffs, and Ngal'ayel Mukau is back from suspension, but Tiago Santos, Nabil Bentaleb, Samuel Umtiti, Andre Gomes and Ethan Mbappe are still unavailable.
Bologna possible starting lineup:
Ravaglia; Posch, Beukema, Lucumi, Miranda; Freuler, Moro; Orsolini, Fabbian, Karlsson; Dallinga
Lille possible starting lineup:
Chevalier; Mandi, Diakite, Alexsandro, Gudmundsson; Andre, Mukau; Zhegrova, Angel Gomes, Sahraoui; David
We say: Bologna 1-2 Lille
Bologna have failed to make the most of their opportunities so far, and are yet to score from 48 attempts; meanwhile, Lille have posted some excellent results despite taking only half as many shots.