The Pernicana–Provenzana Fault System is one of the most active tectonic systems of Mt. Etna and it plays an important role in the dynamic of the eastern flank of the volcano. Earthquakes occurring close to this structural trend have reached magnitudes up to 4.2, sometimes with coseismic surface faulting, and have caused severe damages to tourist resorts and villages in the vicinity of this structure. In the last decade, a large number of shocks, sometimes in the form of swarms, linked to Pernicana–Provenzana Fault System movements have been detected by the permanent local seismic network operating in eastern Sicily. In this paper, we report on the detailed study of the seismic activity occurring during the 2000–2009 time span in the Pernicana–Provenzana Fault System area. Firstly, we located 407 earthquakes using a standard location code and a 1D crustal velocity model. We then applied two different approaches to calculate precise hypocenter locations of the events. In particular, a non-linear code was adopted to obtain an estimate of the a posteriori Probability Density Function in 3D space for the hypocenter location. Moreover, a relative location of correlated event pairs was performed, using the double-difference method. These two different location approaches allowed defining with good accuracy, the most active and hazarding sectors of the structure. The results of these precise locations showed a tighter clustering in the epicenters and in focal depths, in comparison with standard locations. Earthquakes are located along the Pernicana–Provenzana Fault System, and are mainly clustered in two zones, separated by an area with very low rate of earthquakes occurrence, but characterized by the highest energy release. Depths of the foci are very shallow, ranging between the surface and about 3 km b.s.l. Kinematics of the Pernicana–Provenzana Fault System, revealed by the fault plane solutions computed for the most energetic earthquakes, highlights a predominant dip–slip and left strike movements along E–W oriented fault planes, in agreement with field observations.