In this study, the evolution of structure, nanomechanical and tribological properties of polytetrafluoroethylene (PTFE) induced by gamma-ray irradiation with dose up to 20 MGy were investigated, and the frictional failure mechanism after irradiation was also discussed. The structural analyses reveal that the crystallinity degree of PTFE increases significantly with the increase of irradiation dose. The functional groups of COOH, CC and -(CH2)n-are produced due to surface chemical reaction induced by irradiation above 5 MGy dose. High density cracks appear on the surface and both the length and width of the crack propagate with the increase of irradiation dose. Both the nanohardness and Young's Modulus of the irradiated PTFE increase significantly when the irradiation dose is lower than 5 MGy. Further exposure leads to the decrease of nanohardness. The mean friction coefficient increases from 0.035 to 0.12 after 0.3 MGy irradiation and turn to saturation with further increasing irradiation dose. However, after 5 MGy gamma-ray irradiation, the wear rate of PTFE increases significantly, the present of crack on the surface and subsurface accelerates the peeling of the bulk material during the sliding process and results in the wear deterioration.