Abstract: Long-span gantry machine tool for wood movement is the equipment used to complete the different processes. As the main load-bearing structure and moving component, the cross beam has the characteristics of large span, huge weight and large inertial load. High rigidity and light weight are the prominent objectives of its structural design. Aiming at the problems such as difficulty in identifying results of direct topology optimization, the functional sections are established to reduce the dimension of topology optimization by analyzing the load-bearing characteristics. Then, the moving load is simplified to multi-working condition loads, a comprehensive evaluation function is established by compromise programming method, and the mathematical model of topology optimization is established. Finally, multi-objective size optimization is carried out by using NSGA-II genetic algorithm. The results show that the stiffness, strength of the cross beam are increased by 10.15%, 20.25% respectively while the weight is reduced.