Karst geology is widely distributed in China, and water inrush disasters in karst mines have severely restricted the safe production of mines. Water-blocking curtain grouting is the main measure for controlling mine water inrush disasters, and the reasonable determination of curtain thickness is the key to ensuring water-blocking effect and structural stability. At present, curtain design mainly relies on engineering analogy and codes, so a systematic integrated design method combining water-blocking curtain theory and engineering verification needs to be established. Taking the water-blocking curtain for fractured water inrush in a karst mine in Guangxi as the engineering background, this paper systematically conducts an optimal design study on curtain thickness through a combination of theoretical calculation, numerical simulation and field verification. The results show that: ① By establishing a mechanical model of four-edge fixed thin plate suitable for the mining area, the expressions of curtain thickness are derived using trigonometric series solution and polynomial approximation respectively. Verified by engineering data, the calculated curtain thicknesses by the two methods are 10.47 m and 10.62 m respectively, which confirms the consistency and rationality of the curtain thickness setting. ② Based on theoretical results, the 3DEC numerical simulation software is used to analyze the key influencing factors of curtain thickness and their mechanism. The simulation indicates that the curtain with a thickness of 12 m achieves the best comprehensive performance in water-blocking effect, stress state and deflection variation, which is basically consistent with theoretical results. In addition, through comparative analysis of mechanical responses of different curtain shapes, the square curtain presents superior mechanical performance. ③ A water-blocking curtain with a thickness of 12 m was constructed according to the research results. Field borehole coring shows dense grout filling, and field monitoring was carried out. The monitoring data demonstrate that the curtain is safe, stable and effective: the fractured Y01 water runoff zone achieves a water reduction of 4047 m³/d, which effectively validates the rationality of the curtain thickness design. The research results can provide theoretical and technical references for mine water prevention and control under similar geological conditions.