To clarify the deformation and failure law of karst mountain with deep and large fissures under the action of mining and rainfall, by taking the Pusa landslide in Nayong County of Guizhou Province as an example, the instability and failure mechanisms of karst mountain with deep and large fissures under the action of mining and rainfall were discussed through block discrete element numerical analysis. The results show that the overlying strata of the mountain moved down to the mined-out area with the mining of coal seams M10 and M14, and new fraclures developed to the slope surface. Simultaneously, the height of the the fracture zone of the overlying strata in working face increased with the increase of the goaf range. The fracture zone developed to 30 and 40 times the mining height after mining M10 and M14, respectively, and the deep karst fissure expanded to the lower slope. After rainfall and infiltration, the fracture zone of the overlying strata was connected with deep and large karst fissures. The deep and large karst fissures expanded to the slope surface to form a potential sliding surface under the action of pore water pressure, leading to the collapse and slide of the karst slope. Through comparative study, mining is the control factor of the deformation and destruction of the Laoyingyan Mountain, and subsequent rainfall is the main inducing factor of slope instability.