In order to investigate the catalytic activity of cluster Co2Mo2P3 in hydrogen evolution reaction with water molecule, based on the topological principle and density functional theory, the cluster Co2Mo2P3 was calculated and analyzed by Gaussian09 software at B3LYP/Lanl2dz level. According to the frontier orbital theory, the frontier orbital diagram, the energy level difference of the frontier orbital, the energy level difference of the cluster Co2Mo2P3-H and the binding energy of the cluster Co2Mo2P3-H are analyzed, and find that both configuration 3(2) and configuration 4(4) exhibit good and similar reactivity. The result suggests that configuration 4(4) shows good activity both in the hydrogen absorption reaction and in the resolution process after the formation of Co2Mo2P3-H structure, it is the best structural model for the catalytic reaction of Co2Mo2P3 with water.