Aim: To obtain a gene carrier that can effectively deliver loaded therapeutic genes to tumor cells, avoid toxic effects on normal cells and reduce nonspecific adsorption of plasma proteins. Methods:The conjugate of poly(ethylene glycol) (PEG) andMMP2SSP (PEG-MMP2SSP) was covalently coupled to cationized Antheraea pernyi silk fibroin (CASF) through disulfide bond exchange reaction to obtain a PEG-MMP2SSP-modified CASF (CASFMP). Results: The PEG chains were effectively cleaved from the CASFMP by MMP2. CASFMP/pDNA complexes inhibited human fibrosarcoma cell proliferation, and its cytotoxicity to human normal embryonic kidney cells was significantly lower than that of poly(ethylenimine)/pDNA after coculturing with cells for 24h. Conclusion: CASFMP is a promising compound for use in gene therapy.