The solvent resistance performance of organic solvent nanofiltration (OSN) membranes still need to improve for their applications in harsh organic environments. We envisioned that fluorine (F) atoms could enhance the solvent resistance of OSN membranes owing to the high bond energy of C-F bonds. Herein, a kind of novel solvent-resistant F-containing OSN membranes was successfully prepared via interfacial polymerization (IP), chemical crosslinking and solvent activation processes. Mixtures of m-phenylenediamine (MPD) and 5-(trifluoromethyl)-1,3-phenylenediamine (TFMPD) were used as aqueous monomers, and trimesoyl chloride (TMC) was used as an organic monomer. The incorporation of F-containing monomer is proved useful to regulate the surface morphology and the roughness of the OSN membranes. Two folds increase in permeance for ethanol (achieving 41.6 L M-2 h(-1)MPa(-1)) and a rejection of 99.4% for Rhodamine B (479 Da) were achieved at optimal F-containing monomer ratio. Three persistent static immersion tests, in NMP for 90 days (room temperature), in NMP for 10 days (80 degrees C), and in DMF for 31 days (80 degrees C), respectively, and one continuous cross-flow filtration test for 104 h using Rose Bengal (1017 Da)/DMF solution at room temperature demonstrated that the prepared OSN membranes owned an outstanding solvent resistance, proving vast potential in organic solvent separation and purification.