The soluble salts that cause damage to mural paintings in the Mogao grottoes are usually sodium chloride (NaCl) and sodium sulfate (Na2SO4). Of the destructive forces, the crystallization of sodium sulfate is the worst. This article focuses on how sodium sulfate damages the glutenite and ground layers under different temperature conditions and multiple wet-dry cycles. Sodium sulfate has a great ability to penetrate, migrate and crystallize, causing serious damage. The crystallization mechanism of sodium sulfate and the appearance of damage caused by it are quite different from those of sodium chloride. Expansion and erosion are accelerated by increased sodium sulfate concentrations and certain wet-dry cycle times. Among various meteorological conditions, a dry-wet cycle above 40% humidity and the temperature changes below 32.4[degree]C accelerated the damage. Salt expansion test block strength tests show that the intensity of damage caused by salt crystallization is very large. Typical damage characteristics are formation of powders and granular peeling. The work aimed to explore theories aimed at murals protection.