The aim of this study was to investigate membrane synthesis by interfacial polymerization methods, the application of synthesized nano-composite membrane for natural organic matters (NOMs) removal from water, evaluation of fouling mechanism and antifouling properties. Polysulfone (PSf) was selected as a porous ultrafiltration membrane support and interfacial polymerization was done using tannic acid (TA) and Trimesoyl chloride (TMC) with central composite design (CCD). The effects of TA and TMC monomer concentrations, reaction time and post treatment temperature was evaluated. The synthesized membrane was characterized by field emission scanning electron microscope (FESEM), atomic force microscopy (AFM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and water contact angle. Based on the results, the optimum conditions for synthesizing nano-composite were: TA concentration of 0.27 g/L, TMC concentration of 0.22 g/L, reaction time of 68.29 min and temperature of 25.23 °C. The predicted optimum operational conditions were a NOM concentration of 6.429 mg/L; time of 10.931 min and applied pressure of 1.039 bar. The potential applications of the synthesized nano-composite membranes with interfacial polymerization can enhance water treatment.