While surface morphology is the key parameter affecting membrane performance, its exact roles on membrane fouling have not well unveiled. In this study, effects of membrane surface roughness on fouling caused by alginate adhesion were investigated by thermodynamic techniques of the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) approach and density functional theory (DFT). The energy of a single typical alginate chain adhering to rough membrane surface was figured out to be 0.5-3.0 kJ/mol for the first time. Whereas, the related bending energy at typical bending angle was calculated to be over 13.0 kJ/mol based on DFT calculations. The big energy gap suggested that the alginate chain in solution would not change its configuration to fit membrane surface morphology, and tended to directly adhere to membrane surface. The thermodynamic analyses predicted that the direct adhesion pathway was favorable in energy when an alginate chain approaching to rough membrane surface. As a result, as compared to the smooth membrane, rough membrane corresponds to less alginate adhesion and adhesive fouling. Combination of XDLVO and DFT techniques provided not only molecular insights into membrane fouling, but also a new way for fouling research.