As an important part of fuel supply system of diesel engine, the fatigue life of the high-pressure fuel pipe directly affects the normal operation of the engine. The fuel pulse pressure of the high-pressure fuel pipe has a great impact on the vibration fatigue life of the pipe. It has important significance to carry out research on vibration fatigue characteristic of the high-pressure fuel pipe based on fluid-solid coupling method. The fuel pressure pulse of high-pressure fuel pipe is obtained by computational fluid dynamics (CFD) simulation, and the result is used to establish the fluid-solid coupling model of high pressure pipe. The vibration characteristic simulation analysis base on the fluidsolid coupling model can predict the vibration fatigue life of high pressure pipe more accurately. According to the power spectral density (PSD) signal, material S-N curve and the transfer function results, the vibration fatigue lives of two high-pressure fuel pipe are predicted through the cumulative fatigue damage model. The comparative analysis of different vibration fatigue life results can provides guidance for the optimization design of the high-pressure fuel pipe.