The mechanical properties of red and white Pisha sandstone with moisture content were investigated by direct shear test, X-ray diffraction and electron microscope analysis. The particle size distribution, mineral composition and micromorphology of Pisha sandstone were observed, and the influence of structural characteristics of Pisha sandstone on shear strength was also discussed. The results show that moisture content has different effects on the shear strength of red and white Pisha sandstone. The shear strength of red Pisha sandstone increases first and then decreases with the increase of moisture content dominated by the cohesive force, and the shear strength of white Pisha sandstone decreases with the increase of moisture content dominated by the friction and bite force. The main minerals of red and white Pisha sandstone are quartz, feldspar, montmorillonite and calcite. The easy weathering of feldspar, easy water expansion of montmorillonite, and the easy decomposition of calcite lead to the poor mechanical properties of Pisha sandstone. The white Pisha sandstone is composed of coarse sand and a small amount of fine sands. The particles have obvious edges and large pores, which lead to strong friction and bite force among the particles. The red Pisha sandstone is mainly composed of fine sand, and the structure is more compact, so in the sliding process, cohesion is the dominant factor, and the frictional action is less important.