In order to solve the problems of excessive elastic deformation and excessive inertia force existed in the drive mechanism of traditional die-cutting machine, a lightweight drive rod with full symmetrical structure is proposed as the main force bearing component of the drive mechanism based on the kinematics analysis. The elastic deformation and inertia force of the lightweight drive rod are verified by static simulation analysis, and show that the weight of the drive rod is significantly reduced under the same deformation conditions, the traditional one. Further compared with, taking the minimum elastic deformation and lightweight as the optimization objectives, the Non-dominated Sorting Genetic Algorithm-II (NSGA-II) is used to optimize the structural parameters of the drive rod. The results show that under the working conditions of 350 T die-cutting force and 125 r/min rotating speed, the elastic deformation of lightweight drive rod after structural optimization is smaller (the maximum deformation is 0.00988 mm) and the weight is lighter (27% less). The research data presented in this paper can be used as the theoretical basis for future research on die-cutting mechanism. The lightweight drive rod proposed in this study can be used in die-cutting devices with high die-cutting speed and high die-cutting accuracy.