The fluid–solid interaction force shows significant influence on liquid flow at nanoscale. Vast experimental observations in recent literatures have shown that Darcy's law cannot be applied to nanoporous media. In this study, the slip length and effective viscosity are adapted to characterize the nanoscale effect. First, the nanoscale effect is investigated in nanotubes through computational fluid dynamic (CFD) modeling analysis. Slip boundary condition has been studied as an important discrepancy between macroscopic flow and nanoscale liquid flow. The effect of viscosity change becomes more notable with the slip length increasing. Then, the flow equation for pore network modeling is developed to capture nanoscale effect. The results show that the apparent permeability of nanoscale systems is significantly underestimated when slip effect is neglected. The size of the pore throat determines whether the slip effect needs to be considered, and critical diameter of neglecting the slip effect for circular throat is 79.17 Ls. It is necessary to take the variation of effective viscosity into account under slip boundary condition. With the pore throat size decreasing, the nanoscale effect increases. The nanoscale effect is more sensitive to pore throat size under hydrophobic conditions than hydrophilic conditions.