Preparation of novel swelling resistance membrane by interpenetrating an immiscible flexible polyisobutylene (PIB) polymer into a rigid polyamide (PA) network by interfacial polymerization. Due to the force interlocking of flexible PIB, polyamide network has high strength and excellent resistance to methanol. The PA layer was characterized by mechanical strength, attenuated total reflection fourier transforms infrared spectroscopy (ATR-FTIR), small angle X-ray scattering (SAXS), contact angle, field emission scanning electron microscope (FE-SEM) and atomic force microscope (AFM). RO membrane performances were evaluated based on small molecule alcohol (methanol and ethanol) solution of Safranin O. The results show that the flexible PIB interpenetrates well in the rigid polyamide network and improves mechanical strength and swelling resistance. With an increasing concentration of PIB from 0% to 0.30% in the organic phase during the fabrication, the mechanical strength of the PA layer becomes 2.8 times that of the original, and the rejection of Safranin O increased from 95.43% to 99.43%, and the permeability coefficient (B-s) decreased from 5.22 to 0.47.