High-entropy alloy (HEA) is composed of five or more metal elements. It has excellent mechanical properties, tribological properties, corrosion resistance, high temperature resistance and other properties. The friction behavior of FeNiCrCoCu High-entropy alloy was studied using molecular dynamics (MD) simulation method at the nanometer level. The influence of friction depth, temperature, sliding speed and cobalt content on the frictional properties of FeNiCrCoCu High-entropy alloy was studied with the help of LAMMPS and OVITO software. The main research results are as follows: (1) The change in friction force will first go through a growth period, and then gradually stabilize. The fluctuation of its value is due to the release of stress energy caused by dislocations and the accumulation of wear debris. (2) As the friction depth increases, the plowing phenomenon and the accumulation of debris become more obvious and plastic deformation increases. (3) Temperature has no significant effect on the magnitude of friction force and the morphology of the alloy substrate surface. (4) There is an insignificant positive correlation between sliding speed and friction force and sliding speed does not have a significant impact on the amount of debris. (5) With the increase of the content of cobalt, the hardness and friction force of FeNiCrCoCu High-entropy alloy increase significantly at 600 K while the amount of wear debris decreases.