This work deals with the effect of surface roughness parameters on the frictional properties of nanowire-based lubrication systems (NBLS) across Cu surfaces with various topographies. The friction coefficient was discussed in the context of surface roughness parameters including the rms height, inter-island separation and a combined roughness parameter related to the pressure experienced by each nanowire. It was concluded that the rms height of asperity should not be lower than the radius of nanoparticles for effective lubrication. In addition, when the inter-island separation is an integer multiple of the nanowire length, nanowires perform as effective lubricants. Furthermore, the friction coefficient increased when the mean pressure experienced by the nanowires increased. The results obtained in this original study offer some interesting insights into the frictional properties of NBLS as a function of surface roughness parameters. This could lead to a great impact on the selection of nanoparticle-based lubricant aimed at reducing wear and energy losses for various applications.