Combined with the finite element theory, the optimization design of multiple intersecting spheres pressure hull is conducted with the design method based on the test points. Based on the relevant theory of optimization design of test points, 25 groups of test points are determined with the orthogonal test design.The three-dimensional model of multiple intersecting spheres pressure hull corresponding to 25 test points is established with the parameterization modeling method. Based on the finite element theory, its strength and stability are analyzed with Workbench to obtain the maximum stress, critical buckling load, and hull mass corresponding to the parameters of each test point. According to the results of finite element analysis, the response surfaces of maximum stress, critical buckling load, and hull mass related to the spherical center spacing radius ratio, thickness, and cutting arc angle are constructed. Using the genetic algorithm, combined with the constructed response surfaces, the optimization design of multiple intersecting spheres hull is conducted and is checked with Workbench to verify the safety of designed hull.