According to the characteristics of fissure development and strong water yield in the aquifer of bedrock weathering zone overlying S1234 working face in Ningtiaota Coal Mine, based on the theory of elasticity and Bingham rheological equation, the calculation model of horizontal directional grouting borehole stress field and the grouting diffusion model of bedrock weathering zone aquifer are constructed. Considering the influence of horizontal directional drilling stress field and slurry diffusion characteristics, the calculation formula of grouting pressure in the aquifer fissure of bedrock weathering zone is proposed. According to the strength parameters and fracture development characteristics of the weathered bedrock layer, the grouting pressure is determined to be 8.4MPa, taking the 30m thick weathered bedrock layer as the effective diffusion radius of the slurry. Through the rational design of slurry ratio and grouting rate, the effective diffusion of slurry in the bedrock weathering zone aquifer fissure channel is realized. Finally, horizontal hole drilling and underground water drainage test were used to verify the water plugging effect of on-site grouting. The results show that the underground water inflow is reduced from 128m3/h before grouting to 13.8m3/h, and the water plugging effect of roof weathering zone is significant, which provides a reference for water disaster treatment of bedrock weathering zone under similar engineering conditions.