Jinchuan nickel mine is the largest nickel resource production base in China. With the rapid depletion of rich ore resources in Jinchuan No. 2 mine area, it is urgently necessary to mine the hanging wall low-grade ore resources to stabilize the mining area’s production capacity. The process of rich ore mining disrupts the original geo-stress field in the rock mass, causing the deformation and destruction of the hanging wall low-grade ores and surrounding rock mass, seriously affecting the overall stability of the mining of low-grade ore resources. Given the technical difficulties in mining the hanging wall low-grade ores, three technically feasible mining methods have been developed, including downward drift filling combined with subsection medium-deep hole subsequent filling mining method. In addition, the unascertained measure theory is employed to determine the optimal mining scheme. By constructing the whole numerical model of the Jinchuan No. 2 mine area and verifying its reliability, a numerical simulation analysis of the mining effect of the low-grade ore resources mining plan was carried out. It was found that the mechanized panel downward layered large drift cemented filling mining method has the smallest stress concentration and the relative minimum total displacement, which is more conducive to the overall stability of the panel. Based on the practice of mine production, the industrial field test of mechanized panel downward layered large drift cemented filling mining method is carried. Established a full-digital microseismic monitoring system and multi-parameter weight early warning model in the mining area, real-time early warning and countermeasures. The mining site has a loss rate of 7.0% and a dilution rate of 6.5%. The research results can provide technical support for efficient and safe mining of low-grade ore resources or secondary resources and have broad application prospects.