The effects of Cu on the structure and properties of CuxCoCrFeNi were investigated experimentally and compared with the results of molecular dynamics simulations. Experimental results revealed that the alloy's crystal structure transitions from a single FCC to a biphasic FCC as Cu content increases. Mechanical testing indicated that increasing Cu content initially boosts, then reduces the alloy's yield and tensile strength, while elongation consistently increases, demonstrating enhanced plasticity. Additionally, nanoindentation tests further substantiated the notable impact of Cu content on alloy hardness. The nanoindentation simulation results show that the dislocation density increases and then decreases with the increase of Cu content, which explains the change of alloy properties with the increase of Cu content from a microscopic point of view. These findings offer valuable insights for designing and optimizing high-entropy alloys.