The Serie A side clinched their third consecutive European win with a sizzling second-half display that yielded goals from Dario Dainelli, Riccardo Montolivo, Marco Marchionni and Alberto Gilardino.
Adrian Mutu also scored for the home team in the first half while Gergely Rudolf and substitute Adamo Coulibaly replied for the visitors, who remain point-less and have no hope of progressing to the next round.
Second-placed Fiorentina have nine points from four games after their third consecutive European win, one point behind Olympique Lyon, who have now qualified, and five ahead of five-times winners Liverpool.
"We are happy but we have to stay calm and continue to play as we are," Peruvian midfielder Juan Vargas told Sky television.
"We have to stay humble because there are still two matches left to play."
The hosts went out to attack and Romanian Mutu, who scored twice in his side's 4-3 win at Debrecen two weeks ago, gave them a deserved early lead by diving to nod in a Marchionni ball into the box.
Rudolf produced an acrobatic finish to put away a cross from the left before the break, but parity was short-lived.
Full-back Dainelli showed courage to beat keeper Djordje Pantic's fist to the ball and head home before substitute Montolivo skidded in to score and Marchionni chipped in.
Coulibaly took advantage of some poor marking to pull one back but Gilardino completed the rout by heading in a free-kick.
