Failure tests on sandstone specimens were conducted under different confining pressures and seepage pressures by using an MTS triaxial rock testing machine to elucidate the corresponding correlations of permeability and characteristic stress with confining pressure and pore pressure during deformation. The results indicate that permeability first decreases and presents two trends, i.e., a V-shaped increase and an S-shaped trend during the non-linear deformation stage. The greater the seepage pressure, the greater the initial permeability and the more obvious the V-shaped trend in the permeability. As the confining pressure was increased, the trend in the permeability gradually changed from V- to S-shaped. Compared with the case at a high confining pressure, the decrease of permeability occurred more quickly, the rate of change becomes greater, and the sudden increase observed in the permeability happened earlier under lower confining pressures. Within the range tested, confining pressure exerted a greater effect on the permeability than the seepage pressure. In comparison with the axial strain, volumetric strain better reflected changes in permeability during compaction and dilation of sandstone. The ratio of crack initiation stress to peak strength ranged from 0.37 to 0.50, while the ratio of dilation stress to peak strength changed from 0.58 to 0.72. Permeabilities calculated based on Darcy and non-Darcy flow changed within the same interval, while the change in permeability was different.