Enhancing the water permeance and improving the antifouling performance of developing thin film composite (TFC) nanofiltration (NF) membranes remains a great challenge for practical applications. In this work, a novel TFC membrane was fabricated by introducing a new capsaicin derivative (propyl 2-(acrylamidomethyl)-3,4,5-trihydroxybenzoate, PAMTB) into a polyamide (PA) layer during interfacial polymerization for the NF process. The abundant hydroxyl groups in the PAMTB molecules can compete with the amino group in piperazine (PIP) to react with acyl chloride in trimesoyl chloride (TMC), facilitating the formation of a smooth and hydrophilic membrane surface with an enlarged pore size to promote water permeance. Compared to the control TFC membrane, the PAMTB-incorporated membrane exhibited increased water flux from 80 L m-2h-1 to 115 L m-2h-1 and a steady rejection of above 98.0% with 2.0 g L-1 Na2SO4 as the feed solution under a pressure of 5.0 bar. Different measurement methods demonstrated that the TFC-PAMTB membrane exhibited superior antifouling properties and long-term stability. In particular, the permeation flux recovery was approximately 100% after simple hydraulic washing with HA solution as the foulant. This work introduced a new approach to exploit capsaicin-mimic moieties in water treatment applications.