With the gradual improvement of coal mining efficiency, the disturbance of groundwater system caused by the high-intensity mining mode also increases, which is a more severe challenge to the prevention of mine safety and the protection of water resources in mining areas. How to accurately describe the dynamic changes of the groundwater system under mining and quantitatively predict mine water inflow is a major problem in the current research. Based on the full analysis of the response characteristics of groundwater system to the extraction disturbance, this paper forms a kind of method to establish a mine hydrogeological conceptual model that can accurately represent the water inrush process, and uses the MODFLOW non-structural division grid to accurately characterize the formation structure, and finally make accurate water inflow prediction. Taking the Caojiatan Coal Mine in Shaanxi Province, China as an example, a numerical model of unstructured mine water inrush was established for the first time, and the changes of water inflow source and water inflow intensity were quantitatively evaluated. Compared with the traditional water inflow prediction method, it is found that the prediction accuracy is improved by 12%~17% by detailing the response characteristics of complex groundwater system under high-strength coal seam mining conditions. The method is of great significance and promotion value for the comprehensive understanding of the disturbance characteristics of human underground engineering activities, such as coal mining, on the groundwater system, and for accurately predicting water inflow.