A novel approach has been demonstrated to improve the separation performance of thin film composite (TFC) forward osmosis (FO) membranes, which were interfacial polymerized on the surface functionalized porous polymeric substrates. In the new approach, top surface of the polysulfone (PSf) substrates were modified by a novel bio-inspired polymer polydopamine (PDA) through the oxidant-induced dopamine polymerization in a Tris-buffer solution at pH=8.5 in air, over which m-phenylenediamine (MPD) and trimesoyl chloride (TMC) were employed as the monomers for the interfacial polymerization reaction to form a polyamide (PA) rejection layer. This new scheme has revealed that it is possible to fabricate novel TFC-FO membranes with significantly improved water permeability and salt rejection properties simultaneously compared with those constructed on pristine PSf substrates. A high Jw/Js of about 20 l/g (or a low Js/Jw of about 0.05 g/l) can be achieved by using a 2 M NaCl as the draw solution and deionized water as the feed solution in a testing configuration where the active layer facing the draw solution at 23 °C. The PDA surface modification step plays a positive role in the fabrication of TFC-FO membranes, which is realized by producing a hydrophilic smooth membrane surface with smaller surface pores and a narrower pore size distribution for the interfacial polymerization reaction, as well as improving the hydrophilicity of the pore wall inside the substrate. Furthermore, the coated PDA layer could actively interact with TMC monomer during the interfacial polymerization, which may be favorable for the formation of a better quality PA layer with a high salt rejection.