In order to analyze the fatigue life of 4100QBZL diesel engine crankshaft, the coupled multibody dynamics model of crankshaft system was established. The load simulation results of main journal and connecting rod journal under the flexible body model of crankshaft were acquired and the static strength was then checked. Finally, the crankshaft fatigue life prediction was conducted by combining the load spectrum collected from multibody dynamics software, the stress and strain finite element analysis results of the crankshaft under various conditions and the fitted SN curve according to the material properties. The results show that both the crankshaft static strength and fatigue life can meet the design requirements of the project. The life of critical position for crankshaft is beyond 10-13 times, so it is thought that crankshaft fatigue failure will not happen.