The molecular dynamics method was used to simulate repeated nano-friction on a nickel-based single crystal (NBSC) superalloy. The friction force, atomic displacement, wear scar morphology, subsurface defects, potential energy, and other aspects were comprehensively studied to understand the friction mechanism of NBSC during working conditions. The frictional force fluctuated significantly and the coefficient of friction decreased during the repeated friction process. As the friction cycles increased, the wear scars of the gamma' phase deepened, whereas those in the gamma phase became shallower. Simultaneously, repeated friction reduced the volume and number of stacking faults. Additionally, the two phases softened to some extent at higher temperatures, but the phase boundary still had good wear resistance at high temperatures.