Slippage effect and effective stress change are bound to occur in the pressure depletion process of deep shale gas reservoir, both of which play an important role in permeability evolution. It is necessary to investigate their mechanism on seepage. In this paper, the deformation and seepage experiments of shale under the coupling effects of bulk stresses and pore pressures are performed. The results show that pore pressure and in-situ stress have significant effects on the deformation of shallow shale gas reservoirs. The deep high-stress shale is in a compact state, and its compressibility is significantly reduced, which makes the effect of pore pressure on internal fracture deformation can be ignored. As the shale gas reservoir goes from shallow to deep, the slippage effect replaces the effective stress to dominate the shale gas seepage. Under low stress and high stress, the effective stress coefficient κ
of shale permeability are both greater than 1, and their values are 2.90 and 2.95, respectively. This indicates that the assumption of κ
=1 without experimental verification is questionable, and may cause significant deviation to the prediction of shale gas production. Since the formation of micropore structure of shale is closely related to clay particles, the experimental phenomenon of κ
> 1 can be explained by clay-shell model. The linear, quadratic and double-slip Klinkenberg equations are used to correct the slippage effect, and it is found that the relationship between apparent permeability and pore pressure is more consistent with the quadratic function. In the deep high-stress environment, the slippage effect is more obvious with the depletion of pore pressure compared with the change of reservoir effective stress. The slippage coefficient decreases exponentially with pore pressure, and the slippage effect diminishes accordingly at high gas pressure. Finally, by determining the optimal κ
in an effective stress domain, the stress sensitivity index of permeability ξ
, is obtained at different stress stages, and then a new method to quantify the contribution of slippage effect to apparent permeability is proposed.