The highly mineralized mine water is characterized by its complex composition, high salinity, and significant hardness, which leads to the formation of inorganic scales during thermal desalination processes, primarily composed of CaSO₄. Based on the typical composition of highly mineralized mine water, a simulated feed solution containing Ca²⁺, Mg²⁺, Na⁺, Cl⁻, and \mathrm{S}{\mathrm{O}}_{\mathrm{4}}^{\mathrm{2}-} was prepared. The solubility of CaSO₄ in the Ca²⁺-Mg²⁺-Na⁺-Cl⁻-\mathrm{S}{\mathrm{O}}_{\mathrm{4}}^{\mathrm{2}-} system was then investigated using an isothermal dissolution method at temperatures of 40, 50, 60, and 70℃. The results indicate that within the temperature range of 40℃ to 70℃, the solubility of CaSO₄ decreases with increasing temperature, increases with higher MgCl₂ concentration, and decreases with higher Na₂SO₄ concentration. The Oddo-Tomson saturation index method was used to predict the scaling trend of CaSO₄ in the thermal desalination process, and the modified saturation index (SI) equation was obtained. The prediction results of this equation are consistent with the scaling experiment of CaSO₄ on the surface of stainless steel pipe at 65℃. When the saturation index exceeded 0.2, CaSO₄ crystals began to precipitate on the surface of stainless steel tubes in the Ca²⁺-Mg²⁺-Na⁺-Cl⁻-\mathrm{S}{\mathrm{O}}_{\mathrm{4}}^{\mathrm{2}-} system. Finally, scaling experiments using simulated high-mineralized mine water SA and SB were employed to demonstrate the feasibility and limitations of this method in practical mine water applications.