Cellulose derivatives are the earliest and most widely used membrane materials due to its many excellent characteristics, especially chemical activity and biodegradability. However, the hydrophobic properties of cellulose acetate (CA) limited its development to some extent. To improve the inherent hydrophobic and antifouling properties of the CA membrane, CA was successfully modified with dopamine (CA-2,3-DA) through selective oxidation and Schiff base reactions in this work, which was confirmed by 1H NMR and FTIR measurements. And then, the CA-2,3-DA membrane with high water permeability and the excellent antifouling property was prepared by the phase inversion method. Compared with the primordial CA membrane, the CA-2,3-DA membrane maintained a higher rejection rate for BSA (92.5%) while greatly increasing the pure water flux (167.3 L/m2h), which could be overcome the trade-off relationship between selectivity and permeability of the traditional CA membrane to a certain extent. According to the three-cycles dynamic ultrafiltration and static protein adsorption experiments, the CA-2,3-DA membrane showed good long-term performance stability and superior antifouling performance, which was supported by the experiment results including filtration resistance, flux decline ratio and flux recovery ratio. It is expected that this approach can greatly expand the high-value utilization of modified natural organic polysaccharides in separation engineering.