The Group F rivals convene at Stadio Artemio Franchi, with the Viola occupying top spot heading into their penultimate fixture; however, Genk are just two points behind.
Match preview
With Serbian outsiders Cukaricki cut adrift at the bottom of the Group F standings, the final two matchdays will see three clubs battle it out to progress: Fiorentina, Genk and Ferencvaros are all separated by only two points.
The trio have drawn all of their meetings so far, but Fiorentina can travel to Budapest next month with a top-two place secured - if they first see off opponents they came close to beating in Belgium.
Genk twice came from behind to snatch a draw in September's reverse fixture, when centre-back Luca Ranieri bagged an unlikely brace for the Viola, but they now meet the Belgians again with home advantage on their side.
In fact, Fiorentina can be confirmed as group winners - thereby avoiding an extra playoff tie - if they win on Thursday and Ferencvaros fail to take maximum points from rock-bottom Cukaricki.
Europa Conference League runners-up last season, while also impressing on the domestic scene, Vincenzo Italiano's side have lacked such fluency so far this term, losing four of their last five Serie A matches.
That caused Italiano to publicly bemoan his strikers' efforts following Saturday's 1-0 defeat to Milan at San Siro, which was the fourth time Fiorentina had failed to score in the space of a month.
Genk also fired blanks at the weekend, in a 1-0 loss to Standard Liege at Stade de Sclessin, and they sit sixth in the Belgian Pro League as things stand.
While Wouter Vrancken's men cannot go through or be eliminated from the Conference League this week, as they are locked on six points with Ferencvaros, avoiding defeat in Florence is surely essential - particularly if they still have designs on top spot.
There is a significant incentive for teams that claim first place, as they will head straight for the last 16 rather than facing a knockout-round playoff meeting with one of eight clubs demoted from the Europa League.
Having come within a whisker of being crowned Belgian champions last term, being denied by Antwerp in the most dramatic circumstances on the final day, Genk may be a little further off the pace this season but remain a tough team to beat.
The Blauw-Wit have lost just twice in 16 matches since the start of September, drawing half, and they are sure to fancy their chances against a Fiorentina side that often falter in the opposition area.
Fiorentina Europa Conference League form:
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Fiorentina form (all competitions):
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Genk Europa Conference League form:
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Genk form (all competitions):
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Team News
In the first of two home fixtures within the space of three days, Vincenzo Italiano is set to make several changes to the Fiorentina team that started against Milan last time out.
Luca Ranieri is likely to return after serving a one-match suspension, while young full-back Michael Kayode could complete his comeback from an ankle injury. Up front, M'Bala Nzola should replace Lucas Beltran, who has yet to score a Serie A goal since signing in the summer.
Dodo and Gaetano Castrovilli are out of action for the rest of the year, but Italiano should have an otherwise full squad to select from.
Meanwhile, Wouter Vrancken was without one of his key players on Saturday, as Daniel Munoz withdrew from the Genk squad shortly before kickoff. The Colombian defender returned from international duty just in time, but a bout of flu puts his participation at Stadio Franchi in some doubt.
Blau-Wit captain Bryan Heynen should start in midfield, with Joseph Paintsil, Tolu Arokodare and Andi Zeqiri - all of whom have scored once in the Conference League this season - vying for selection in the final third.
Fiorentina possible starting lineup:
Terracciano; Kayode, Milenkovic, Ranieri, Biraghi; Lopez, Mandragora; Gonzalez, Barak, Brekalo; Nzola
Genk possible starting lineup:
Vandevoort; El Ouadhi, Cuesta, McKenzie, Arteaga; Heynen, Galarza, El Khannouss; Bonsu Baah, Zeqiri, Paintsil