An anti-fouling hybrid membrane was prepared by incorporating Ag-SiO2 nanohybrid into a polysulfone (PSf) matrix. The addition of Ag-SiO2 can significantly improve the hydrophilicity, separation property, anti-fouling ability, and especially anti-bacterial activity of hybrid membranes. The optimum performance of the Ag-SiO2/PSf hybrid membrane is achieved when the concentration of Ag-SiO2 is as low as 0.45 wt%. Compared with PSf membrane and SiO2/PSf hybrid membrane, the Ag-SiO2/PSf hybrid membrane displays the best overall properties. The excellent performance of the Ag-SiO2/PSf hybrid membrane can be attributed to the well-tailored structure and unique property of Ag-SiO2 nanohybrid, where nanosized Ag (∼5 nm) can densely and uniformly disperse on the surface of silica spheres. The obtained membrane could be a promising material for water treatment.