Abstract: In this study, controlled variable tests were carried out on the MRH-3 high-speed ring-on-block wear test machine, in order to investigate the tribological properties of polyamide 66 under dry friction, wet friction and various water lubrication conditions. The wear mechanisms were obtained by analyzing topographies of worn surfaces. It is found that polyamide 66 had good tribological properties under the linear velocity of 0.51 m/s and the pressure of 1.17 MPa. Orthogonal tests were further developed and the results showed that the best tribological property was obtained at a linear velocity of 1.29 m/s and the pressure of 0.95 MPa. This study provided the experimental basis to the application of polyamide 66 to the material of water-lubricated bearings and guide rails.