Recently the use of peptides in bee venom (PBV) for cancer therapy has attracted considerable attention. However, PBV's extensive use is prohibited by its intense hemolytic activity. In this study, the sterically stabilized liposomal PBV (PBV-SL) was prepared using soybean phosphatidylcholine, cholesterol, and cholesterol-PEG-COOH. The humanized antihepatoma disulfide-stabilized Fv (hdsFv25) was reengineered, expressed, and coupled to sterically stabilized liposomes using the N-hydroxysuccinimide ester method. The hdsFv25-immunoliposomes (SIL [hdscFv25]) were immunoreactive as determined by ELISA assay. PBV-SIL [hdscFv25] can kill SMMC-7721 cells in vitro with higher efficiency than nontargeted liposomes. PBV-SIL [hdsFv25] displayed high antitumor activity and resulted in a significant reduction in tumor size compared to nontargeted liposomes and PBV. These results indicated that this strategy should be applicable to applicable in the treatment of other cancers.