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Cellulose membrane has been widely used for bioseparation and blood puri?cation but suffers from fouling issue and insuf?cient biocompatibility. Surface grafting of zwitterions onto membrane surface can effectively alleviate this issue. Current grafting methods are mostly based on free radical polymerizations and have limitations of multi-step process, the requirement of inert atmosphere and inevitable ?ux decline. Herein we put forward a simple method for cellulose membrane (CM) zwitterionization. The modi?cation was carried out via a one-step method based on the alkoxysilane condensation reaction using three silane coupling agents including (3-carboxypropylbetaine-propyl)-trimethoxysilane(CPPT),(3-sulfopropylbetaine-propyl)-trimethoxysilane (SPPT), and (3-sulfobutylbetaine-propyl)-trimethoxysilane (SBPT). Membrane surfaces were characterized by ATR-FTIR, XPS, SEM, water contact angle (WCA) and streaming potential. Membrane mechanical performance, pore size and its distributions were measured. The antifouling property, hemocompatibility and cytocompatibility of the membranes were evaluated by protein adsorption, platelet adhesion, cell attachment and MTT assay experiments. The results show that sulfobetaines and carboxybetaines were successfully grafted on the CM surface. The obtained zwitterions-grafted membranes show excellent resistance to protein adhesion, platelet adhesion and cell attachment. More importantly, the biocompatibility of the CM membrane was retained.