Pre-stretching is a reliable and widely used method for improving the properties of metallic materials. Current research on effect of pre-stretching on material properties has primarily focused in macroscopic-scale, with little attention given to the effects of nano-scale pre-stretching on material properties. In this study, molecular dynamics simulations were employed to pre-stretch FCC-structured FeCoCrNiCu materials. Tensile simulation, nano-indentation simulation, and nano-scratching simulation were conducted on HEAs under different pre-strain conditions (5%, 7%, and 10%) to investigate the effects of pre-stretching on the mechanical and tribological properties of FCC-structured high-entropy alloys at nanoscale. The results indicate that pre-stretching does not significantly affect the yield strength of HEAs. This is primarily because pre-stretching does not lead dislocations formation within the HEAs. During nano-indentation, pre-stretching accelerates the plastic deformation response of HEAs, prolongs the time interval between drastic pop-in events, and relieves stress concentration. Pre-strain of 5% and 7% caused strain softening in HEAs, while 10% pre-strain resulted in strain hardening in HEAs. During nano-scratching, HEAs with 10% pre-strain exhibited the best tribological properties, with 10% pre-strain reducing the friction coefficient and wear atoms of HEAs. However, 7% pre-strain reduced the wear atoms of HEAs but did not significantly affect the friction coefficient. The 5% pre-strain did not significantly affect the tribological properties of HEAs. Pre-stretching did not change the plastic deformation mechanism of HEAs, which remained dominated by dislocation motion during nano-scratching. The reason that pre-stretching affects the mechanical and tribological properties of high-entropy alloys is that it increases interatomic distances and reduces the stacking faults energy of HEAs. As pre-strain increases, stacking faults energy decreases, which also explains why pre-stretching exhibits a size effect on the mechanical and tribological properties of HEAs. This work provides a scientific theoretical basis for understanding the mechanical and tribological behavior of HEAs under pre-strain conditions. It also offers insights and references value for understanding the effects of pre-stretching on the properties of metallic materials.