The flow of argon liquid in an asymmetric nanochannel with smooth and rough wall is investigated by molecular dynamics method. Considering the relationships of related factors which include characteristic dimensions, the number and the dense arrangement pattern of nanostructure, the effects of surface topography on fluid flow and interface slip are probed. The results show that the variation of the surface topography height has a significant influence on the fluid flow and interface slip. However, the effect of the variation of topography width is greatly related to the number and dense arrangement pattern of nanostructure. Surface topography causes an increase in interfacial resistance and more reduction in velocity slip at the rough wall, which even results in the forming of sticky boundary condition. The effect of non-uniform interface wettability of rough wall on the flow behavior and slip at the solid–liquid interface is investigated as well. The results show that the influence of non-uniform interface wettability on the flow in the hydrophobic channel is more obvious than that in the hydrophilic channel. Hydrophobic substrate with hydrophobic nanostructures has a smaller interfacial hydrodynamic resistance than that with hydrophilic nanostructures, which makes the average velocity and velocity slip become greater. Obviously, non-uniform interfacial wettability strengthens the effect of surface topography on the fluid flow and interface slip. It is possible to achieve effective velocity slip and obtain drag reduction by applying the non-uniform wettability of nanostructures under the same surface topography. © 2020 Elsevier B.V.