Nano-scale Au/Cu multilayers were investigated by nano/microindentation. It was found that the hardness of the multilayers increases with decreasing individual layer thickness (λ), and shear band deformation can occur more easily in the multilayer with small λ. For comparison, the same experiments were also performed on Cr/Cu multilayers with the same layer structure. The results show that the Cr/Cu multilayer can be more effective in resisting shear band deformation than the Au/Cu multilayer. Finally, the λ dependence of shear band deformation and the difference between plastic deformation behaviors of the two multilayers were analyzed based on dislocation plasticity.