In this study, we present a unique surface modification method for a water desalination membrane to control the surface fouling via titanium dioxide (TiO2) nanopillar pattern imprinting. The patterned membranes showed significantly improved fouling resistance for both organic protein and bacterial foulants compared to the nonpatterned membranes. The hydrophilicity of TiO2 used as a pattern material affects the improvement of chemical antifouling resistance of the membrane. Fouling behavior was also interpreted in terms of the topographical effect depending on the relative size of foulants to the pattern dimension. Moreover, the computational fluid dynamics simulation intimates that the overall and local shear stress enhancement on the patterned surface could affect the foulant deposition behavior on the membrane.