Abstract: Human beta defensin 2 (HBD2) is a small antimicrobial peptide,which is able to inhibit the proliferation of multiple cancer cells.In this study,HBD2 was linked to a single chain of the Her-2 antibody fragment (4D5 scFv) by genetic engineering,and the soluble HBD2-4D5 was expressed successfully by the small ubiquitin-like modifier (SUMO）molecular chaperones in E.coli.HBD-4D5 was purified using the combination of Ni-NTA Sepharose FF,digestion by specific SUMO protease and Sephadex G-25,the purity was higher than 95% with a yield of 15 mg/L. The fusion HBD2-4D5 showed significant antibacterial activity against E.coliK12D31 andStaphylococcus aureus (ATCC25923), suggesting that the activity of HBD2 was reserved. Also, HBD2-4D5 demonstrated selective binding activity to SK-BR-3, a Her-2 over expressed breast cancer cell line. This finding provides foundations for further investigation for the treatment of the HER-2 over expressed breast cancer.