The strength and deformation behavior of reservoir rock saturated in brine is of great interest to scientists and engineers in geological carbon dioxide (CO2) sequestration in deep saline aquifers. However, the mechanical behavior of brine-saturated sedimentary sandstone under triaxial compression with respect to different confining pressures has not been fully investigated, in particular in view of the numerical simulation. In this study, experimental study and numerical simulation were carried out on brine-saturated sandstone specimens to explore the mechanical properties, micro-crack or acoustic emission and energy dissipation in sandstone with various salinities of brine. First, laboratory uniaxial compression tests were conducted on brine-saturated sandstone specimens and the enhancement in strength and elastic modulus were observed with increasing brine salinity. The scanning electron microscopy results showed NaCl crystals deposited in the pore space, which provides an evidence of strength and modulus variation of sandstone after brine saturation. Second, micro parameters in PFC3D numerical model were calibrated for each brine salinity condition, and the numerically simulated results were compared with the experimental results. The numrical results agreed well with the triaxial compression test results, indicating the rightness and reasonability of calibrated models. Finally, the entire evolution of number of micro crack, cracking and energy dissipation in the numerical specimen were analyzed in PFC3D.