Abstract: Membrane distillation MD technology occupies an important position in the zero-discharge treatment process system of high-mineralization mine water due to its unique advantages, such as low operating pressure and the efficient utilization of low-grade heat sources. It is one of the key technical units for constructing an economical and efficient treatment process. However, the lack of high-performance MD membranes has hindered its industrial application. The vapor-induced phase separation (VIPS) technique was used to replace the traditional liquid-induced phase separation technique to prepare hydrophobic microporous polyvinylidene fluoride (PVDF) membranes, which were then applied to the membrane distillation technology for treating high-mineralization mine water. By coordinately regulating parameters such as the temperature, humidity, and exposure time during the VIPS process, the optimization of the membrane structure and performance was achieved. Using characterization methods such as scanning electron microscopy, porosity testing, and pore size analyzer, the effects of different parameter conditions on the membrane structure were monitored. The synergistic effects among multiple factors were comprehensively analyzed by the response surface method. High-salt simulated water and the actual high-mineralization mine water from the Ningdong Mining Area were used to test the actual performance of the optimized VIPS membrane during the membrane distillation process. The results indicate that: Elevating temperature accelerates the phase separation rate during VIPS, reduces the formation of nodular structures on the membrane surface, and facilitates the development of larger pore sizes and higher porosity. However, excessively high temperature constrains the enhancement of porosity. Increased humidity promotes the intrusion rate of non-solvents in VIPS, which contributes to enlarged pore sizes, elevated porosity, and improved membrane flux; conversely, excessively high humidity results in pore closure. Exposure time primarily governs the progression of phase separation: insufficient phase separation occurs with overly short exposure time, whereas pore collapse is induced by overly long exposure time. An appropriate exposure time helps to form a uniform and high-performance membrane. There are also interactions of different degrees among the parameters. The synergistic effect between temperature and exposure time is the most significant, followed by that between temperature and humidity, while the interaction between humidity and time is weak. Finally, the VIPS membrane was prepared using the optimized parameters of a temperature of 40 ℃, a humidity of 70%, and an exposure time of 15 min, and its treatment performance was evaluated using a direct contact membrane distillation device. The test results showed that the average fluxes of the membrane reached 14.75 L/(m²·h) and 14.03 L/(m²·h), respectively, and the rejection rate was above 99.9%, remaining stable throughout the test period. The scanning electron microscopy images of the membrane surface before and after the test showed no obvious attachment of pollutants, and the contact angle measurement data remained stable at around 110° before and after the test, indicating that the membrane has good anti-wetting and anti-fouling capabilities and exhibits excellent performance.