The structure of diffuser vanes has a significant influence on the performance of centrifugal compressors. To research the influence of diffuser vane thickness on the overall performance and internal flow condition of the centrifugal compressor. This paper takes a centrifugal compressor as the research object. By changing the diffuser vane thickness, and using three-dimensional fluid simulation technology to carry out simulation research. The results show that the thinner diffuser vanes can greatly improve the efficiency, flow rate and outlet temperature of the centrifugal compressor. For internal local fluid characteristics, thin diffuser blades have lower internal heat load. However, the local flow of fluid is not consistent with the change of vane thickness.