Abstract: To reduce the cost of filling and the potential safety hazards caused by the accumulation of waste rock in the waste dump, the waste rock−slurry cemented filling process is adopted in Xifeng Phosphorite Mine. Through a combination of research methods such as the response surface method, technical and economic analysis and microstructure characterization, the sensitivity of the main influencing factors was analyzed. Besides, the filling ratio parameters were optimized, and the mechanism of the hydration products was revealed. The research results indicated that the sensitivity of the influencing factors of the uniaxial compressive strength of the filling body is in the order of slurry concentration>cement to fly ash mass ratio > ash to rock ratio. Under the conditions of 55% slurry concentration, ash−to−rock ratio of 7∶20, and cement−to−fly ash ratio of 87∶100, the strength of the filling body reaches 10.60 MPa, saving a total cost of over 1.31 million yuan/100,000 t of filling material per year. The pore structure of the optimized filling bodies is filled with hydration products such as calcium silicate (C−S−H), calcium hydroxide (CH) and alumina (AFt) in combination with fly ash that is not involved in the hydration reaction. The microstructure is dense and has strong resistance to external compression damage. The research results can provide a theoretical basis and technical support for the safe mining of open−pit to underground filling.