Analysis of the stress distribution and fatigue life of the broken shaft of the drive shaft during the lifting process of the ESP is of great significance for improving the reliability of the drive mechanism and ensuring the continuous and stable operation of the ESP. Aiming at the broken shaft part of the drive shaft, the mechanical characteristics analysis and fatigue life prediction method of the drive shaft under multi-load action was proposed. The results of numerical simulation and field test analysis show that when each load acts alone, the stress area of the pin hole is distributed in strips along the radial direction and the stress distribution is relatively uniform, and the stress area of the internal thread gradually weakens from top to bottom along the radial direction, and the maximum stress is most affected by the torque, and the bending moment caused by the dogleg is the smallest; when the loads are combined, the axial force has the greatest influence on the stress distribution of the pin hole and the internal thread, and the maximum stress is less than the allowable stress, so the reason for shaft breakage is not brittle fracture caused by overloading; the fatigue life of the internal thread is significantly shorter than that of the pin hole, which provides a basis for the optimal design of the transmission shaft.