A p-vinylbenzyl sulfobetaine was grafted from cellulose membrane (CM) using surface-initiated atom transfer radical polymerization for blood compatibility improvement. Surface structure, wettability, morphology, and thermal stability of the CM substrates before and after modification were characterized by attenuated total reflectance Fourier transform infrared spectra, X-ray photoelectron spectroscopy measurement, water contact angle measurement, atomic force microscopy, and thermogravimetric analysis, respectively. The results showed that zwitterionic brushes were successfully fabricated on the CM surfaces, and the content of the grafted layer increased gradually with the polymerization time. The blood compatibility of the CM substrates was evaluated by protein adsorption tests and platelet adhesion tests in vitro. It was found that all the CMs functionalized with zwitterionic brush showed improved resistance to nonspecific protein adsorption and platelet adhesion, even though the grafting polymerization was conducted for several minutes.