Red-bed soft rock in the drawdown area on bank slopes of landslide easily disintegrates upon exposure to water, and its properties experience comprehensive deterioration, which will cause bank slope instability. To better study disintegration mechanism of the red-bed soft rock, a series of laboratory tests were conducted in this paper to investigate the disintegration characteristics, durability and hydrogeochemical process of red-bed argillaceous siltstone under drying-wetting cyclic conditions. Experimental results showed that, with increasing number of drying-wetting cycles, red-bed argillaceous siltstone gradually disintegrated, from initial appearing the cracks on the surface of the samples to large particles gradually breaking up into small fragments. Significant changes in grain size distribution, and the durability index of the samples progressively decreased. Microstructural analysis showed that the size and distribution of pores and cracks in the sample surface significantly increased, such that the sample surface became disordered and complicated. Notable changed in concentrations of ions in the soaking solutions indicated continuous mineral dissolution and loss during the cyclic drying-wetting. Based on the results obtained from the experiment, it is concluded that the disintegration of samples undergoing drying-wetting cycles was the result of the synergistic action of water and temperature. To be specific, the dissolution of calcite, albite, gypsum, montmorillonite and kaolinite during the wetting procedure, which promotes the decrease in mineral content and increases in pores and cracks. The increases in temperature and the dehydration shrinkage of sample during the drying procedure accelerated the disintegration of the samples.