Victory in France puts Les Dogues within touching distance of a place in the playoffs, where they would face either Union Saint-Gilloise or Slavia Prague.
Match preview
Aiming to reach the group stage in their first Champions League campaign under Jose Mourinho, Fenerbahce are under pressure to produce a comeback, after losing last week's first leg 2-1 in Valenciennes.
Though Lille could not play at Stade Pierre-Mauroy due to the Olympics, they still edged out Mourinho's men with a late winner, leaving Fener with work to do back on home turf.
The Istanbul club's three other competitive matches this season have all ended in victory, beating Swiss side Lugano 6-4 on aggregate in the Champions League's second qualifying round and then winning their Super Lig opener at the weekend.
Overcoming the disappointment of losing in France, Fener saw off Adana Demirspor thanks to a first-half goal from veteran striker Edin Dzeko, laid on by new boy Allan Saint-Maximin at Sukru Saracoglu Stadium.
Like Lille - who they have now failed to beat in three meetings, including two in the 2010-11 Europa League - the Yellow Canaries lost in last term's Conference League quarter-finals, but they are intent on earning a seat at Europe's top table this season.
After conceding a 79th-minute equaliser in a close-fought first leg, Edon Zhegrova's late winner could prove invaluable to Lille's hopes of progressing into the final round of Champions League qualifying.
Zhegrova starred in their run to the Conference League's last eight last season, and his contribution puts them in the driving seat ahead of a tough trip to the Turkish capital.
After leading LOSC to fourth spot in Ligue 1 last term, former boss Paulo Fonseca departed for AC Milan, and new head coach Bruno Genesio is now overseeing their latest attempt to reach UEFA's top club competition.
It has been three years since Les Dogues made it through to the group phase, and this year's expanded format would ensure at least eight high-profile games through to January.
However, Tuesday's second leg and a potential playoff must still be negotiated, either side of Saturday's league opener away to Reims.
Fenerbahce Champions League form:
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Fenerbahce form (all competitions):
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Lille Champions League form:
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Team News
Jose Mourinho made a handful of changes for the league win over Adana Demirspor, but Bright Osayi-Samuel and Alexander Djiku are among those who could be brought back into Fenerbahce's starting lineup on Tuesday.
Fener's front line will be led by experienced marksman Edin Dzeko, who already has five goals from four games this season, with support supplied by another seasoned campaigner, ex-Ajax schemer Dusan Tadic.
Morocco striker Youssef En-Nesyri recently signed from Sevilla and is likely to be used as an impact substitute.
Meanwhile, Lille's Jonathan David has been linked with a transfer for several months now, but the Canada international is still at the club and should start in Istanbul.
Though Leny Yoro and Yusuf Yazici both left the club this summer, Thomas Meunier has joined after a spell in Turkey with Trabzonspor and will start at right-back.
Despite scoring LOSC's stoppage-time winner last week, Edon Zhegrova may again be consigned to the bench, before making a cameo appearance during the second half.
Fenerbahce possible starting lineup:
Livakovic; Osayi-Samuel, Djiku, Oosterwolde, Kadioglu; Yuksek, Szymanski; Kahveci, Tadic, Saint-Maximin; Dzeko
Lille possible starting lineup:
Chevalier; Meunier, Diakite, Alexsandro, Gudmundsson; Santos, Gomes, Andre, Haraldsson; Cabella; David
We say: Fenerbahce 2-2 Lille (Lille win 4-3 on aggregate)
Both sides boast plenty of European experience and attacking flair, but the onus is on Fenerbahce to get back into the tie, so they may be caught out on the counter.