Polyamide reverse osmosis (RO) membranes suffer performance decay when exposed to free chlorine because of their unique chemical structure. The decay limits their lifespan and increases operating cost. Herein, the secondary interfacial polymerization method was performed, for the first time, using isophthaloyl chloride (IPC) as the chain-terminating reagent, to eliminate the negative effect when the unreacted amino groups interact with chlorine. The surface zeta potential of the as-prepared membrane remained almost constant over a wide pH range, which greatly demonstrated the high conversion ratio of the end-capping procedure. However, neither the surface morphology nor the separation properties were conspicuously influenced. Because of the absence of the terminated amino groups in the polyamide layer, the IPC-modified membrane exhibited significantly improved chlorine resistance, particularly at high pH. Its desalination performance remained unchanged as the total chlorine exposure approached 10 000 ppm·h, whereas only 80.3% of the NaCl was rejected by the unmodified membrane under the same conditions. Such SIP technology can be applied directly to the commercial SW30 seawater desalination membrane, making it more tolerant to free chlorine. Overall, our results strongly proved the IPC-assisted end-capping process as a promising, practicable, and scalable technology for enhancing the chlorine resistance of an RO membrane.