To investigate the effect of hydro-mechanical coupling characteristic in low-permeability hard rocks during the excavation of groundwater-sealed energy cavern and hydraulic engineering tunnels or chambers, triaxial compression tests were conducted on engineering granite under different confining and seepage pressures. The mechanical properties, such as the strength and deformation parameters, of granite under hydro-mechanical coupling condition were studied. The permeability of the granite under different stresses first decreases, then stabilizes, and then increases significantly until the final abrupt change, and the inflection point of the abrupt change in permeability tends to be in advance as the confining pressure increases or the seepage pressure decreases. Based on the statistical damage theory and test result, combined with the Mogi-Coulomb strength criterion, a hydro-mechanical coupling statistical damage constitutive model that considers the rock damage threshold and the initial compaction effect was proposed, and the proposed mechanical model was verified based on the test results under different confining and seepage pressures. The proposed mechanical model was further applied to predict permeability catastrophes during rock fracturing and achieves good results. This study provides a theoretical basis for the prevention and control of hydro-mechanical coupled disasters in rock engineering.