Carbon capture, utilization and storage (CCUS) is one of the key technologies to cope with global climate change and has received a lot of attention from all countries in the world. Supercritical carbon dioxide (SC-CO2) can be utilized to displace methane in shale gas reservoirs, due to its low viscosity, high diffusivity, and high density. However, the injection of SC-CO2 may cause to a series of physical and chemical interaction with shale rocks, which leads to the irreversible changes of shale properties in physics and mechanics. In order to investigate the changes of shale mechanical properties with SC-CO2 interaction, the shale specimens were treated with SC-CO2 soaking under different time, pressure, and temperature, then a series of uniaxial compression tests were carried out on the treated specimens. Elastic modulus, Poisson's ratio and peak strength were selected as the response factors, a second-order response surface model was fitted to analyze the interaction between mechanical properties and soaking conditions. The results indicated that the single factor influence of soaking time is the greatest, followed by the pressure and temperature. The multiple factors influence of soaking time and pressure is the greatest, followed by the soaking time and temperature, and finally the soaking temperature and pressure. The results confirmed that the interaction of soaking time, pressure, and temperature has significant impact on the mechanical properties of shale rock. The results can help to understand the evolution of shale mechanical properties with SC-CO2 interaction under different soaking time, pressure, and temperature, and it can also provide the basis for the exploitation of shale gas using SC-CO2 displacement.