Abstract: So far, the researches on the degradation of macroscopic strength of rock under cyclic wetting-drying conditions in the course of reservoir operation mainly focus on simulations of single environmental conditions without considering the combined actions of slope stresses, wetting-drying cycles and seepage water pressures. The triaxial test system of soft rock in the drawdown areas is developed independently to simulate the combined actions of slope stresses, wetting-drying cycles and seepage water pressures. The red sandstone from Majiagou landslide is selected as the study object. The uniaxial and triaxial compression tests on the red sandstone are carried out, and the failure modes are analyzed after each wetting-drying cycle. Meanwhile, the variation of microstructure and clay mineral content of red sandstone undergoing different numbers of wetting-drying cycles is always explored by means of the scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results show that with the increasing number of wetting-drying cycles, the peak compressive strength of red sandstone decreases gradually. In the first four wetting-drying cycles, the peak compressive strength decreases obviously. After the sixth wetting-drying cycle, the decline trend of the peak compressive strength decreases gradually. With the increasing of wetting-drying cycles, the cohesion of red sandstone decreases gradually either, and the cohesion decreases a lot during the first four wetting-drying cycles. The reduction extent of cohesion is obviously reduced in the sixth to eightth wetting-drying cycles. The friction angle of red sandstone decreases with