Abstract: Karst geology is widely distributed in China, and karst water gushing has become a huge disaster and challenge for the safe production of limestone mines. Taking the large-flow water inflow of a karst sunken open pit mine in Guangxi as the research object, aiming at the characteristics of complex geological conditions, large concentrated water inflow and high flow rate of the mine, the karst development characteristics, data analysis and geophysical exploration methods are used to preliminarily delineate the mine runoff zone area and water source. After that, the specific location of the karst pipeline at the Y01 extra-large water gushing point of the mine was accurately found through drilling, cross-hole CT and tracer connection test. On this basis, the mine water gushing treatment technology and process were studied and implemented. The research shows that: ① In view of the characteristics of large flow and high flow rate in complex karst sunken open pit mines, a comprehensive treatment system of water gushing in karst mines is proposed and implemented, which is “discontinuous curtain closure + key channel exploration and plugging + slurry-stopping cushion to control flow and reduce speed.” According to the inhomogeneity of karst development, the idea of discontinuous curtain plugging fissure water gushing area is put forward. A slurry-stopping pad flow control device was designed for the concentrated water inflow of large-flow karst pipelines. The flow control can effectively reduce the flow velocity in the key water passage, which provides an important condition for the effective retention and deposition of grouting materials and the successful plugging of the project. ② The key hole refers to the drilling hole that directly exposes the karst water gushing pipeline or has strong connectivity with the water gushing pipeline and plays a major role in grouting and water plugging. In this paper, two key holes were successfully found for the large water inflow of Y01 karst pipeline type in the mine, both in the south of the mine. One is a short-distance borehole with a linear distance of about 50 meters from the water inflow point, which is referred to as the near hole, and the other is a long-distance borehole with a linear distance of about 150 meters from the water inflow point, which is referred to as the far hole. The simultaneous grouting process of two key holes, near hole and far hole, is adopted in the field. The near hole is mainly grouted with aggregate, and the far hole is only grouted with slurry. The near hole aggregate can not only reduce the water flow in the pipeline, but also play a better role in retaining and depositing the far hole slurry, and can be used as a plugging material to enhance the function. The far hole can ensure the length and effect of plugging due to its wide radiation range and sufficient slurry diffusion. The simultaneous grouting of near hole and far hole is an effective combination process for rapid plugging of large flow water gushing in pipeline. ③ After the implementation of the project, the Y01 super-large water gushing point with a concentrated water inflow of 71 200 m³/d in the mine was completely blocked, and the total water reduction was 84 300 m³/d (including discontinuous curtain grouting plugging), which ensured the normal and safe mining of the mine, greatly reduced the cost of pumping and drainage, and protected the surrounding environment and groundwater resources, with significant economic and social benefits. The research results can provide important theoretical technology and experience for the treatment of water inrush disaster in karst mines in China.