Since the railway vehicle structure has lots of parameters and several complex constraints, this study establishes a method for structural parameter optimization based on sensitivity analysis and surrogate models. Fatigue crack problem of the equipment cabin bottom cover of the EMU is taken as an example to optimize its structural parameters. First, establish the finite element (FE) model of the bottom cover and compare it with the bench test results to verify the accuracy of the load and restraint conditions. The sensitivity analysis method is used to determine the main parameters. The input samples are obtained by Latin hypercube sampling method, and the output samples are obtained by the method jointly developed by ABAQUS+Python and the surrogate model between the input and output samples is obtained by fitting, and its accuracy is verified. According to the design requirements, the optimization objective function and constraint conditions are established, and the optimization result is obtained by optimization algorithm. The results were substituted into the FE model for verification. The results show that the maximum equivalent stress of the bottom cover is reduced from 126.7 MPa to 78.9 MPa under a cyclic aerodynamic load of ±4 kPa, which is 37.7% optimized, and the effect is significant. This method avoids the iterative optimization of the FE model and improves the optimization efficiency.