Large high clearance self-propelled sprayers were widely used in field plant protection due to their high-efficiency operation capabilities. Influenced by the characteristics of field operations such as high power, heavy weight, high ground clearance, and fast operation speed, the comprehensive requirements for the ride comfort, handling stability and road friendliness of the sprayer were increasingly strong. At the present stage, the chassis structure of the high clearance selfpropelled sprayer that attaches great importance to the improvement of comprehensive performance still has the problems of severe bumps, weak handling performance and serious road damage in complex field environments. Therefore, this paper proposes an optimization design method for hydro-pneumatic suspension system of a high clearance self-propelled sprayer based on the improved MOPSO (Multi-Objective Particle Swarm Optimization) algorithm, covering the entire process of configuration design, parameter intelligent optimization, and system verification of the high clearance self-propelled sprayer chassis. Specifically, chassis structure of the hydro-pneumatic suspension suitable for the high clearance self-propelled sprayer was designed, and a design method combining the improved MOPSO algorithm based on time-varying fusion strategy and adaptive update with the parameter optimization of hydro-pneumatic suspension based on this algorithm was proposed, and finally the software simulation and bench performance verification were carried out. The results show that the optimized hydropneumatic suspension has excellent vibration reduction effect, and the body acceleration, suspension dynamic deflection and tire deflection were increased by 16.5%, 9.9% and 0.9% respectively, compared with those before optimization. The comprehensive performance of the hydro-pneumatic suspension designed in this study is better than that of the traditional suspension.