Membrane-based technologies are increasingly used for water and wastewater treatment; however, biofouling, the adhesion of microorganisms to the membrane and subsequent formation of biofilm, remains a major obstacle in real applications. In this study, we report a novel method to fabricate a highly antibiofouling membrane by grafting quaternary ammonium compounds (QAC) onto a silica-decorated membrane via alkoxysilane polycondensation reaction. A controlled architecture was created by initially coating polydopamine (PDA)/poly-ethylenimine (PEI) layer, followed by in situ synthesizing a hydrophilic silica nanoparticle layer through silification reaction and then immobilizing QAC on the silica-decorated membrane to form an antibacterial surface. Although the QAC modified membrane exhibited comparable surface roughness, hydrophilicity and water permeability with the pristine membrane, the former displayed clear antibacterial effects against both Gram-positive and Gram-negative bacteria compared to the pristine membrane, i.e., similar to 93% and similar to 92% inhibition of S. aureus and E. coli, respectively. The excellent biofouling resistance imparted by the QAC layer was further confirmed by filtration experiment, showing lower water flux decline compared to the control. In addition, QAC-modified membranes exhibited high stability during repeated chemical cleaning cycles. This grafting protocol for QAC provides a new dimension to modify a wide range of water and wastewater treatment membranes for mitigating biofouling.