The Uruguay international gifted his side the lead from the spot, before the attacking midfielder effectively put the match to bed before the break.
Edinson Cavani gifted the Partenopei the lead early on when he converted a penalty. Marek Hamsik then decided the game when he doubled his side's lead some 10 minutes before the interval.
Napoli started the match with attacking intentions and got the early goal the team was after in the 15th minute. Milan Milanovic was called for handling the ball inside his own area, and Cavani had no trouble finding the net from 12 yards to make it 1-0.
The home side continued to dominate play after the opener and Hamsik eventually doubled Napoli's lead in the 35th minute after some good work Goran Pandev.
Both Napoli and Palermo created a number of chances in the remainder of the game, but no more goals were to be seen at the San Paolo.
Napoli currently sits third in the Serie A table with 58 points from 36 games. The team resumes league action against Bologna on May 6.
Palermo is the league's 15th-placed team with 42 points. It hosts Chievo on Sunday.
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