Novel thin film nanocomposite (TFN) nanofiltration membrane with tunable physico-chemical properties and separation performances was fabricated by incorporating the copper benzene-1,3,5-tricarboxylate (CuBTC) nanoparticles with different concentrations (ranging from 0 to 0.75 wt.) in the polysulfone (PSf) substrates, followed by the interfacial polymerization process of trimesoyl chloride (TMC) and piperazine (PIP) to establish top selective layer. Charaterization results show that both chemical and physical properties of poly(piperazineamide) selective layer was altered when PSf substrate was modified by CuBTC. The introduction of CuBTC nanoparticles improved the hydrophilicity of the TFN membranes (from 70.25° to 59.02°) and promoted formation of more linear structure of poly(piperazineamide) entangled with �COOH pendant groups. By incorporating 0.25 wt. of CuBTC into the PSf substrate, the resultant membrane flux was enhanced by 22 with MgSO4 rejection remained at 97.31. Furthermore, a notable increment of rejection against NaCl could be attained by increasing the CuBTC content in the substrate. This could be explained by the Donnan potential effect occurred on the more linear structures of poly(piperazineamide) surfaces, which results in an increase in the selectivity of monovalent salts. Moreover, the incorporation of CuBTC rendered the TFN membranes to exhibit good anti-fouling property against bovine serum albumin. © 2019 The Institution of Chemical Engineers