Caojiatan Coal Mine produces a large amount of coal gangue solid waste in the mining process, and the ground accumulation will cause problems such as waste of land resources and environmental pollution. The comprehensive utilization of coal gangue resources has certain limitations and the utilization rate is not high. To solve the problem, a set of large-scale grouting and filling processes for coal gangue was designed in this paper, and the field application was carried out. The system processed the "more crushing and less grinding" ground crushing and pulping scheme of "three-stage crushing + ball milling", and injected the coal gangue slurry into the falling zone of the underground goaf through the adjacent grouting and filling process, which realized the harmless and large-scale treatment of coal gangue. The process flow of the system included the crushing, pulping, pumping, and pipeline transportation of coal gangue to ensure the quality of the slurry and the efficient operation of the system. The industrial application showed that the diffusion effect of the slurry was good, the accumulation height and diffusion radius met the expectations, which effectively reduced the environmental pollution in the mining area, reduced the cost of coal gangue transportation, and realized the large-scale disposal of coal gangue. In the later stage, the grouting and filling process will be continuously optimized, so as to improve the utilization rate of underground fillable space and improve the large-scale grouting and filling capacity, so as to provide reference for the grouting and filling technology of coal gangue underground.