Crankshaft is one of the key parts of the diesel engine. Several causes would be lead to the failure of the crankshaft. A novel strength analysis method is used for crankshaft high cycle fatigue simulation of the diesel engine based on flexible multi-body dynamics in this paper. In order to investigate the fatigue strength of other parts of the diesel engine at the same time, a complete coupled dynamic model of diesel engine crankshaft and block is built and coupled dynamics simulation is carried out. Then dynamics calculation results of each part is extracted for high cycle fatigue analysis and the reliability research of the crankshaft, The simulation results show that, the minimum safety factors of the crankshaft is 1.301, it meet the strength requirements, the safety factors of the block and the cap could be calculated at the same time. These suggest that this method can guide the design of the diesel engine crankshaft and has gained significant importance in practical study.