Abstract: The main vacuum system is an important auxiliary system of hefei cyclotron, which provides vacuum environment for the cyclotron to produce high quality particle beam. In this paper, based on the design parameters of the main vacuum system of the cyclotron, through the calculation of true air load, flow conductivity, pumping speed and equipment selection, the whole scheme of vacuum system is designed. The molecular flow simulation software Molflow+ was used to simulate the vacuum pressure distribution in the middle plane of the cyclotron. Finally,the feasibility of the design is verified by experiments.