Wolfsburg, who had won five of their last six games in all competitions, must now score four goals in the second leg on April 23 in Naples to have any hope of progressing to the semis.
Gonzalo Higuain put Napoli ahead after 15 minutes against the run of play from a pass by Dries Mertens, despite a hint of handball, before Hamsik struck eight minutes later.??
The Slovakian forward beat Wolfsburg’s offside trap to latch on to Higuain’s curling pass and score.
Hamsik’s second goal on 64 minutes was a simple finish after a poor pass in the Wolfsburg defense allowed Jose Callejon to snatch the ball and set up the forward.
Manolo Gabbadiani added a fourth with a 77th-minute header, but the host pulled one back three minutes later when Nicklas Bendtner scored to boost Wolfsburg’s slim hopes.
Elsewhere, defending champions Sevilla came from a goal down to beat Zenit St Petersburg 2-1 at home, with substitute Denis Suarez scoring the winner with an 88th-minute volley from the edge of the area.
Winger Alexander Ryazantsev had put Zenit ahead on 29 minutes, scoring off his own rebound after his first effort was saved by Sergio Rico. The Russian visitors looked on course for victory until the 73rd muinute, when Carlos Bacca’s header leveled the score.
In Ukraine, Fiorentina rescued a 1-1 draw away to Dynamo Kiev, with Khouma Babacar’s stoppage-time leveller saving the Italian team from a third straight defeat in all competitions.
Jeremain Lens had given Dynamo a first-half lead with a deflected effort from 20 yards into the far top corner.
Club Brugge’s Australian goalkeeper Matthew Ryan made some smart saves to deny Dnipro a 0-0 draw in Belgium, keeping Brugge in contention for a first European semi-final since 1988.