With the expansion of the modern chemical industry into the nanoscale, two-dimensional (2D) graphene-based membranes have gained significant attention in alcohol/water mixture separation due to their large lateral dimensions and nanometer thickness. However, the interface-induced effect is poorly explained for a further understanding of the confined transfer mechanism of mixed fluids through 2D nanochannels. In this work, we proposed a theoretical framework considering the interfacial adsorption effect and effective transfer path of mixed fluids to describe the selectivity accurately of different alcohol/water systems (ethanol/water, n-butanol/water, and isopropanol/water) in 2D graphene-based membranes. Our results demonstrated that the low friction resistance of water contributed to the high permeation of water and the high selectivity of water/alcohol. Finally, we also discovered that there was a beneficial permeation for alcohol rather than water within a certain range of slit widths in the graphene channel, and the different slit widths for the graphene and MXene channels would have their specific separation performance for ethanol/water mixture due to the change of wettability and confined degree.