The bridge structure of bridge crane is a typical welded structure, and fatigue cracks often appear in the weld area of the main beam during daily service. In order to ensure the service safety of the crane, a multi-level sub model of the dangerous crack region was established based on the multi-scale finite element analysis method. The thermal structural coupling welding finite element model was established on the secondary sub model, and the whole welding process was simulated and analyzed. The influence of post weld heat treatment on residual stress was simulated. Combined with the multiaxial critical interface method, a fatigue analysis method using the strain amplitude as the multiaxial damage parameter was constructed, and the fatigue performance of the dangerous crack region was evaluated. The results show that the proposed method transforms the overall fatigue problem of the structure into the fatigue problem of the local welding position, which not only increases the calculation efficiency, but also considers more influencing factors of the fatigue details, and provides a certain reference for the fatigue life assessment and life extension of the crane weld.