Fouling is regarded as the bottleneck in membrane filtration process. One of the practical strategies to decrease fouling is the use of advanced anti-biofouling membrane material. In this study, mesoporous silica (MS) particles was synthesized as inorganic fillers, and fabricated with polyethersulfone (PES) to achieve nanocomposite membranes with antifouling properties by phase inversion method. The effect of the MS particles on the microstructure and properties of the resulting hybrid membranes were investigated by scanning electron microscopy (SEM), thermal gravitational analysis (TGA), and ultrafiltration (UF) experiments. The results indicated that the nanocomposite membrane with 2% MS exhibited excellent hydrophilicity, water permeability and good antifouling performance. In addition, the TGA results showed that the introduction of the MS particles improved the thermal stability of the nanocomposite membranes. The protein adsorption on the membrane surface decreased significantly from 45.8 μg/cm² to 21.4 μg/cm² when the MS content increased from 0% to 2%. Most importantly, the protein UF experiments revealed that the incorporation of MS particles reduced membrane fouling, especially irreversible fouling, which reduced dramatically. No benefit was gained from higher MS content (4%), which resulted in significant particle agglomeration.