With the rapid development of cities, the automated and intelligent garbage transportation has become an important direction for technological innovation of sanitation vehicles. In this paper, a vehicle-mounted trash can-handling robot is proposed. In order to reduce the cost of the robot and increase the loading capacity of the intelligent sanitation vehicles, a lightweight design method is proposed for the truss structure of the robot. Firstly, the parameters of the robot that are related to the load are optimized by multi-objective parameter optimization based on particle swarm optimization. Then, the material distribution of the truss structure is optimized by topology optimization under multiple load cases. Finally, the thickness of the truss structure parts is optimized by discrete optimization under multiple load cases. The optimization results show that the mass of the truss structure is reduced by 8.72%, the inherent frequency is increased by 61.08%, and the maximum stress is reduced by 10.98%. The optimization results achieve the goal of performance optimization of the intelligent sanitation vehicle, and prove the feasibility of the proposed lightweight design method.