4100QB diesel flexible multi-body dynamics model was built by employing the modal synthesis technique in the software Adams, and the application of multi-body dynamics modeling method in simulation of engine main bearing force was carried out. By comparing the simulation results of different models, the effects of flexibility of cylinder block and crankshaft, installing method of engine and the elasticity of shaft coupling were also discussed. The results showed that the flexibility of cylinder block and crankshaft, as well as the installing method of engine, played an important role in main bearing force calculation. The influence of elastic shaft coupling was negligible in simulation of main bearing force. Finally, the simulation result was validated by the measuring engine block vibration acceleration.