Non-equilibrium molecular dynamic simulations have been carried out to study the effect of the interface wettability on the pressure driven flow of a Lennard–Jones (LJ) fluid in a nanochannel. The results show that the hydrodynamic boundary condition at the solid–liquid interface depends on both the interface wettability and the magnitude of the driving force. For a LJ fluid in a nanochannel with hydrophilic surfaces, the velocity profiles have the traditional parabolic shape. The no-slip boundary condition may break down when the driving force exceeds a critical value that overcomes the interfacial resistance. In such a case, the MD results show a pattern of an adsorbing layer sliding along the solid wall. For a LJ fluid in a nanochannel with hydrophobic interfaces, the results show that a gap exists between the liquid and the surface, resulting in almost frictionless resistance; the velocity shows a plug flow profile and the slip length is not constant but depends on the driving force. Furthermore, it is found that the non-uniform temperature and pressure profiles near the solid walls are owing to the effect of interface wettability.