Because of the transition from nanoscale to macro-scale in multi-scale pores, the dominant mechanism of gas flow in shale would be transformed between Darcy flow, Knudsen diffusion and other flow mechanisms. This phenomenon combined with gas adsorption in shale matrix makes the calculation of shale gas permeability more complicated. Therefore, to determine the comprehensive influence of effective stress and gas flow mechanisms on permeability at the laboratory scale has a significant impact on the accuracy of permeability and production assessment in real-life shale gas recovery. In this study, the pulse-decay method was used to measure the gas permeability of helium and carbon dioxide in organic-rich shale slices under different confining pressures. The results show that Knudsen diffusion has a significant positive effect on shale gas permeability at low pore pressure, and its strength is inversely proportional to pore pressure. Supercritical carbon dioxide under high pore pressure under high confining pressure can reduce the maximum adsorption capacity of shale matrix and increase its apparent permeability. The apparent permeability has a completely opposite trend with the change of effective stress at different pore pressure region, and the effective stress coefficient appears non-single values at this time, which is mainly caused by the change of gas flow mechanism due to the change of pore pressure.