Using a unique multi-scale simulation approach combining an atomic scale simulation of silicon nanowires (SiNWs) oxidation with an interfacial roughness characterization technique and the non-equilibrium Green's function (NEGF) calculation, the interfacial roughness effect on the transport characteristics was investigated. The calculated interfacial roughness, such as the root-mean-squared (RMS) roughness and correlation length was found to be in good agreement with the previous experimental work. The RMS roughness and correlation length increased linearly during the oxidation process. The NEGF calculation result revealed the decrease of the mobility with the increase of the charge density in the oxidized SiNW with 10 nm diameter.