A high-flux thin film composite (TFC) hollow fiber nanofiltration (NF) membrane was fabricated using a barrier layer of polypiperazine amide synthesized via interfacial polymerization (IP) on a previously prepared dual-layer (PES/PVDF) hollow fiber substrate, which was synthesized via the two-step TIPS/NIPS method. The permeability of the TFC membrane was smaller by an order of magnitude than that of the substrate, which was due to the formation of a thick barrier layer. The structure of the barrier layer was controlled via the addition of cyclic ethers (dioxane, oxolane and trioxane). By increasing the polarity of cyclic ethers, the thickness of the barrier layer and the dense layer was reduced due to the piperazine concentration in the organic phase. Comparing with oxolane and trioxane, the addition of dioxane resulted in a narrower pore size as that of the conventional IP process, which was ascribed to the narrow IP reaction zone via the immiscibility of interface. With the addition of dioxane up to 2 wt%, the barrier layer became thinner, the pure water flux of the resultant membrane was improved and the dextran rejection was maintained. The novel hollow fiber NF membrane has a permeability of 16.6 L m−2 h−1 bar−1, a MWCO of 330 Da and a tensile strength of 10.3 MPa. This membrane had a higher rejection of total organic carbon and a lower rejection of total dissolved solids of the secondary effluent from a petrochemical industry plant, which proves the potential of this membrane in municipal, agricultural and industrial wastewater treatment.