In order to enrich diaphragm design theory of reciprocating diaphragm pump so as to extend diaphragm fatigue life, a numerical simulation analysis is carried out on the liquid end of a diaphragm pump, and the motion characteristics of diaphragm and the influences of related parameters on the stress in it and the motion itself are investigated throughout. Because the diaphragm is deformable and driven by a unsteady pressure in the liquid end, fluidstructure interaction has to be taken into account in the simulation. The results show that the fluctuation amplitude of stress in the diaphragm is very high in a cycle of diaphragm motion, namely the maximum peak stress is as high as more than five times the minimum peak stress. The stress concentration region is located at the diaphragm edge. It has been observed that this region frequently is subject to fatigue damage in applications. When a piston stroke is less than 50 min-1, the diaphragm stress is little affected by it; or the diaphragm can experience a significantly increased stress. The ratio of pump displacement to diaphragm capacity should be lower than 85%, otherwise the diaphragm stress increases very sharply. The methods adopted can handle the change in computational domain caused from the motion of the piston and diaphragm quite well. As a result, an analysis of fluidstructure interaction has been realized for the suction and discharge processes of a diaphragm pump.