Abstract: In order to solve the problem that the key parts of the down-hole drilling rig are prone to fatigue damage, the flexible multi-body dynamic model which can reflect the mechanical characteristics of the down-hole drilling rig working device was established by using Lagrange equation and mode superposition method. Using virtual prototyping technology and ADAMS simulation platform, the dynamic analysis of the working device was realized. The stress spectrum of the key parts of the working device of the down-hole drilling machine was obtained by using the measured load spectrum. Based on the nominal stress method, the fatigue damage assessment was realized. The results showed that the stress of fatigue focus could be accurately obtained by the dynamic simulation of flexible multi-body considering the motion attitude of working device, drilling shaft pressure and rotary torque. The most dangerous position of fatigue damage was the hinge of each oil cylinder and welding part of drill arm and the root of hinge support. The stress, fatigue damage and fatigue life of each fatigue focus point were obtained by flexible multi-body dynamics simulation, which could provide a reference for the structural strength improvement and lightweight design.