In order to study dynamic response characteristics and swing-arm fatigue strength of heavy hydraulic modular trailer, a rigid-flexible coupling multi-body dynamic model of trailer was established based on finite element analysis method and rigid-flexible multi-body dynamics theory. The model was simulated with excitation signal by road roughness and verified by vibration experiment results. Dynamic response simulation analysis of trailer was carried out with different operational conditions, as the road roughness and trailer speed. The stress time histories of swing-arm, which are necessary for fatigue analysis, were calculated by using finite element analysis method with dynamic load, as the results of multi-body dynamics simulation. Fatigue life of swing-arm were predicted based on local stress-strain analysis method. The calculation results show that, stress concentration positions of swing-arm appears at cross section of fracture failure location and stress level has entered into plastic state. With operational conditions of trailer on B grade, C grade and D grade roads, the fatigue life of risk points are greater than the service life of trailer. However, on sinusoidal uneven roads, the fatigue life of risk points decreases obviously with the augmentation of sinusoidal amplitude and trailer speed. Reasonable operating conditions, which could enhance trailer’s operation security and transportation efficiency, are proposed from swing-arm fatigue life simulation results.