Geological hazards, particularly water inrush, pose frequent challenges in tunnel constructions within karst regions. Drawing from the engineering experiences in addressing multiple large-scale water inrush hazards in the Dejiang tunnel, a combined method of field investigation and theoretical analysis was employed for qualitative and quantitative analyses of water inrush mechanisms. The regional geological investigation highlighted the formation of strong and weak aquifers due to alternating weak limestone and mudstone in the synclinal strata, creating favorable conditions for large-scale karst conduit. Atmospheric precipitation water connects karst cavities through groundwater-eroded karst conduit, establishing a recharge system for water inrush hazards. Three empirical formulas are adopted to investigate the influence of rainfall on the tunnel’s actual water inflow. Importantly, it was found that considering only the influence of rainfall or surface water cannot reasonably predict the inflow in this area. The disaster’s primary causes are attributed to the heavy rainfall, karst conduit, underground river, and weak strata, which have contributed to the persistent nature of water inrush events. The principle of “drainage and blockage” was used to address the issue of water inrush. Proposed remediation strategies during construction, including the innovative membrane bag high-pressure grouting, have proved to be effective in addressing the connected karst conduits. The drainage and blockage effects were achieved by installing drainage pipes during the grouting reinforcement process. Finally, the water pressure-resistant structure was employed to enhance the stiffness of the lining. As validated by monitoring data, the measures serve as crucial methods to guarantee the safety of tunnel structures, effectively prevent water inrush and amplify the ecological benefits of water-rich areas.