The winding force of the wire rope exerting on the ultra-deep mine hoist drum is intricate in the multi-layer winding process. During the long-term operation process of the hoist drum structure, the degradation of materials and structure damage with time will cause fatigue failure of the drum structure. Therefore, it is necessary to carry out the research of fatigue life of the hoist drum structure under the actual working conditions in the multi-layer winding process. On the basis of the theory of plates and shells, the ultra-deep mine hoist drum was regarded as the rotational symmetric shell under uniform pressure. A mathematical model was set up for the force acting on hoist drum structure. Through analyzing load composition of the drum, dynamic models were established for full load lifting and no-load descent of the steel wire rope on the basis of the dynamics principle of hoisting system, and the dynamic load of the drum structure was determined. The stress-time history curves of the drum in the whole working cycle were obtained through the strength analysis of drum structure in the working process. Based on S-N curves with different survival rates and cumulative damage theory, the fatigue life of the drum structure under different load was analyzed. The results indicated that the maximum equivalent stress both occurred in the constant speed stage on the process of full load lifting and no-load descent, and the maximum equivalent stress appeared in the middle part of supporting wheel and supporting ring of inner wall of the drum. The fatigue life of the drum structure at given survival rate was closely related to the workloads. The research provides theoretical support for mechanical analysis and the scientific design of hoist drum under complicated working conditions in the multi-layer winding process.