Polysulfone-zinc oxide mixed matrix membrane (MMM) was fabricated. A polyamide layer was formed on the top surface of the membranes using interfacial polymerization process. The properties and structure of the membranes were investigated and the membranes were used for desalination in reverse osmosis process. Cross-sectional images of the membranes substrate showed that the addition of zinc oxide to the polymer matrix resulted in a denser structure and increased the thickness of the sponge-like layer near the lower surface of the membrane. The addition of zinc oxide to the polymer matrix decreased the surface contact angle of the membrane with water, thereby increasing the hydrophilicity of the membrane. The pure water flux of all membranes reduced at the beginning of the process and after 60 min remained almost constant at the values of 19.50 (Lm-2h-1) and 30.20 (Lm-2h-1) for the membrane made with plain polymer and the MMM, respectively. In the reverse osmosis process, the water flux of the membrane fabricated using plain polymer was 9.70 (Lm-2h-1) which increased by 39% and reached to 13.50 (Lm-2h-1) by the addition of zinc oxide nanoparticles. The salt rejection of plain polysulfone membrane was 92.5% which increased to 97.21% with the addition of zinc oxide to the polymer matrix. The addition of zinc oxide nanoparticles to the polymer matrix significantly decreased the water permeability to salt permeability ratio (B/A) from 40.54 to 14.35 (kPa).