Novel flat-sheet thin-film composite membranes for nanofiltration were fabricated through interfacial polymerization of natural polymer sericin and trimesoyl chloride (TMC) on porous polysulfone support membrane. The preparation parameters including pH of aqueous phase, reaction time, curing temperature, curing time, sericin content and TMC concentration were investigated. The properties of the resultant membrane were characterized in terms of surface chemical structure, morphological structure, surface zeta potential, pure water flux, molecular weight cut-off (MWCO), pore size and rejections to different solutes including electrolytes and organic anionic dyes. It was found that the obtained sericin–TMC composite membranes had smooth and amphoteric surfaces with an isoelectric point at pH about 4.1. The membrane with a MWCO of 880g/mol had a pure water permeability of 11.9l/m 2 hbar and exhibited a salt rejection order of MgCl 2 (22.5%)<MgSO 4 (40.5%)≈NaCl (40.8%)<Na 2 SO 4 (95.4%) at neutral pH. The dye removal tests indicated that the obtained membrane could effectively reject the organic anionic dyes at neutral pH with good anti-fouling property, especially for the dyes with relatively higher molecular weight and/or more negative charge. Moreover, compared with the commercial nanofiltration membrane NF270, the developed sericin–TMC composite nanofiltration membrane possessed better antifouling property.