As the fatigue life of a piezoelectric actuator is relative to the service life of a piezoelectric pump, this paper carries out a fatigue life-related research. First, times of stress cycle corresponding to the ultimate stress is experimentally acquired when Pb(Zr, Ti)O3 (PZT-5)ceramics suffers from the fatigue failure under an electro-mechanical coupling field. The number of samples selected at different levels of stress in the above experiment are discriminated and corrected by using the coefficient of variation. After data processing, a p-S-N double logarithm curve and its linear regression equation are obtained with the safety life at different levels of stress under conditions of 95% degree of confidence and 99.9% livability calculated respectively, which offers important and necessary data for the fatigue life calculation of piezoelectric actuator. Finally, the fatigue life of the piezoelectric actuator of a certain resonance-type air pump is calculated to be 4461 h with safety factor 1.25 by using ansys and hypothesis of fatigue damage accumulation. These results perfect the technical parameters of this air pump and the fatigue data, and the calculation method can be applied to the fatigue calculation of PZT-5 actuator in other kinds of piezoelectric pumps.