Liquid nitrogen (LN 2 ) fracturing is a promising new technology for unconventional reservoir simulation because it can effectively solve problems related to low permeability, low brittleness, and water shortage. The present work conducted a series of permeability and strength property-related experiments to evaluate the effect of LN 2 cooling on the permeability and mechanical characteristics of anisotropic shale. The main findings of the study are as follows: (1) The influence of the bedding direction on the permeability of anisotropic shale cannot be eliminated by LN 2 cooling. LN 2 cooling could effectively increase the initial natural damage and the pore space of anisotropic shale, possibly increasing the volume of reservoir stimulation and provide more channels for the seepage and migration of oil and gas. (2) After LN 2 cooling, the strength and brittleness of shale are obviously reduced, leading to the decrease in the ability of shale to resist deformation and failure, thereby helping to decrease the initiation pressure of reservoir stimulation. (3) The brittleness of shale will markedly increase during cryogenic fracturing, thus helping to form more complex fracture networks. Based on the present research, LN 2 fracturing has obvious advantages compared with hydraulic fracturing in increasing the volume of reservoir stimulation. The results of this study are instructive for understanding the synergistic mechanism of LN 2 fracturing and evaluating the effectiveness of reservoir simulation.