In order to study the variation of the rock physical property parameter and fluid flow parameter during the development of low-permeability reservoir，a new stress sensitivity predictive model for permeability and threshold pressure gradient in the low-permeability reservoir has been derived theoretically combined with the non-linear seepage feature based on the fractal theory of core accumulation model and mechanics of materials. The variation of permeability and threshold pressure gradient versus the effective stress with different mechanical parameters was quantitatively analyzed. Validity of the stress sensitivity model was verified through comparison between theoretical model result and those of available experimental data. The research results show that：the permeability decreases and the threshold pressure gradient increases as the effective stress increases，and the normalized permeability and threshold pressure gradient has a better power function relationship under the effective stress. Stress sensitivity of permeability and threshold pressure gradient is closely relative to the mechanical parameters of rock，higher Young’s modulus presents a relative weaker stress sensitivity of permeability and threshold pressure gradient，and lower Poisson’s ratio exhibits a more stress sensitive threshold pressure gradient and permeability under the same Young’s modulus. The model could accurately predict the stress sensitivity of permeability and threshold pressure gradient，thereby offer a theoretical base and guide for flow rule research and design for production performance in the low-permeability reservoir．