In order to enrich the design theory of stable pressure chamber and solve the problem of insufficient life of the diaphragm between stable pressure chamber and diaphragm pump fluid,here,ZMB240 piston diaphragm pump was taken as the study object to establish a simplified diaphragm pump’s 3-D finite element analysis model. With FSI module of Workbench platform,two-way fluid-solid interaction analyses were performed for the diaphragm pump under working conditions with initial pressure of 0.3 MPa,0.4 MPa,0.5 MPa,0.6 MPa and 0.7 MPa,respectively to monitor the diaphragm’s maximum displacement and equivalent stress variations within a cycle. The simulation results showed that the diaphragm deformation decreases with increase in initial pressure of stable pressure chamber,and all diaphragm deformations under different initial pressures reach the maximum at time t=0.031 8 s; stress fluctuation of the diaphragm is great within a motion period,and the maximum stress is 4 times of the minimum one,the diaphragm end edge is the stress concentration area.  Through studying,a reasonable numerical simulation method to predict stress and displacement variations of stable pressure chamber diaphragm was obtained to guide the design of stable pressure chamber diaphragm and provide a reference for stable pressure chamber design of diaphragm pumps.