Cross-line operation that can improve the utilization of railway equipment and transportation efficiency is expected to be the development of the future, and the key to realizing this is to guarantee the dynamics performance of high-speed trains operating on different railway lines. To this end, this study focuses on determining the parameters of a suspension system for a high-speed train equipped with semi-active dampers. Multi-body dynamics method is used to establish a mathematical model of a high-speed vehicle, and a numerical integration method is applied to calculate the system response. An improved genetic algorithm adopting the dynamic Hamming distance, dynamic crossover, and mutation coefficients is integrated into the numerical simulation process to determine the parameters. Based on the numerical analysis, the optimized damping values for various hydraulic dampers in their passive modes are obtained. Finally, an experimental validation based on roller-rig and field loop-line tests is performed, and the test results verify the effectiveness of the optimized parameters. Thus, the study findings can serve as a reference to enhance the realization of cross-line operation.