We report the fabrication and characterization of a novel organic/inorganic hybrid ultrafiltration membrane with anti-fouling and self-cleaning properties. Nanoscale TiO2 clusters were grafted on the side chains of a poly(aryl ether sulfone) matrix containing trifluoromethyl and carboxyl groups (PES-F-COOH) using a silane coupling agent. Separation efficiency, fouling behavior, and self-cleaning property of the TiO2/PES-F-COOH hybrid ultrafiltration membrane were investigated by dead-end filtration experiments using a polyacrylamide foulant solution. Analysis of the membrane chemistry showed that grafting TiO2 on the side chain of the PES-F-COOH resulted in homogeneous dispersion of TiO2 clusters in the polymer matrix. The hybrid UF membrane exhibited significant self-cleaning efficiency. Specifically, water flux following polyacrylamide fouling was 53% recovered after membrane exposure to UV irradiation, which is attributable to photocatalytic degradation of the organic foulants by TiO2. We further demonstrated the anti-photocatalytic ageing property of the hybrid UF membrane, indicating resistance to decomposition of the membrane polymer matrix by photocatalytic oxidation. Our developed method can serve as a versatile platform for the development of anti-fouling and self-cleaning hybrid membranes or functional materials for a wide range of applications.