Fiorentina look forward to secure their place in the UEFA Champions League knockout rounds as they host a Lyon side that has already qualified.
The last time Fiorentina made it through to the last 16 was a decade ago when they qualified at the expense of an English club, Arsenal FC. A Viola win would also eliminate five-time champion Liverpool from contention, no matter how the English side fares in its game against Debrecen.
Prandelli will be hoping his side will avoid making the same mistakes they made in their surprising 3-2 home defeat to Parma on Saturday. The result saw them drop to sixth in the Serie A standings.
The Tuscan outfit will have to overcome the absence of attacking duo Adrian Mutu and Stevan Jovetic. Both have notched three goals apiece so far in Europe's elite club competition but have failed to recover from their respective injuries and continue to remain sidelined.
With the absence of these two forwards, Fiorentina rely on striker Alberto Gilardino, who scored twice at the weekend . Prandelli welcomes back Per Kroldrup, who has recovered from the flu and Riccardo Montolivo, who missed Saturday's game through suspension.
Despite Fiorentina seeking a third straight home success, unbeaten Lyon will have plenty of motivation to win.
The French giants, who beat Fiorentina 2-1 in Florence last season, know that maximum points against the Viola would assure them top spot in the group.
Claude Puel's side go into the encounter having missed a chance to move two points clear at the top of Ligue 1 after being held to a surprise stalemate by bottom lying Grenoble.
The visitors will be without midfielder Jeremy Toulalan and defender Francois Clerc, both out injured.
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Fiorentina reached the last 16 of the UEFA Champions League for the first time in a decade after overcoming Olympique Lyonnais in Florence, a first-half penalty by Juan Vargas ensuring the Serie A side qualified from Group E with a match to spare.
Cesare Prandelli had urged his team to take the initiative by sealing the victory that would spare them a nervous night on Matchday 6 at Liverpool FC, who won 1-0 at Debreceni VSC, and Fiorentina responded with a spirited first-half display, hitting the woodwork twice before scoring on 28 minutes.
A sell-out crowd of over 35,000 witnessed Fiorentina's historic achievement as they also became the first Italian representatives to qualify for the knockout round this year.
Mario Santana almost put them ahead in the 11th minute with a fine control and volley from the edge of the penalty area, which struck Hugo Lloris' right-hand post. The ball bounced out to Alberto Gilardino, who instinctively poked the ball back towards the goal, but the Lyon goalkeeper showed equally sharp reactions to push his effort wide for a corner.
Fiorentina continued to probe and they were rewarded in the 27th minute when Lyon defender Aly Cissokho unnecessarily hacked Marco Marchionni down inside the area to give away a penalty. The Viola midfielder had cut in well from the right, but Cissokho's team-mate Cris was covering and about to put the ball behind for a corner when the full-back lunged in from behind to leave the referee no choice but to award the spot-kick.
With first-choice penalty takers Adrian Mutu and Stevan Jovetic both injured, Vargas took responsibility to score his first goal of the season at the Stadio Artemio Franchi, placing his penalty into the top left-hand corner of the goal to put the Viola in front.
The prodigious talent of Pjanic looked Lyon's most likely route back into the contest, and the 19-year-old twice tried his luck from distance early in the second period.
The greater momentum was with the Gigliati, however, and they almost doubled their advantage when Gilardino dragged his attempt wide after being picked out by Marchionni, who was then denied by a last-ditch tackle from Cissokho when released by Santana.
Lyon intensified their attempts to equalise with two more dangerous Pjanic free-kicks both finding only the wall. Frey then made impeccable saves to deny Jean Makoun and Lisandro Lopez as the home side held on to take their place alongside their opponents in the next round.