Abstract: Objective 　To determine whether t ransferrin-polyethylenimine ( Tf-PEI), a tumor-targeted DNA carrier, can be used to deliver the IL-12 gene into the nude mouse model of human osteosarcoma, and to observe the effect of gene therapy. Methods 　Using Tf-PEI as the vector, deliver murine interleukin-12 (mIL-12) gene into human osteosarcoma cells. Free t ransferrin was used to inhibit Tf-PEI, and the influence was observed. Tf-PEI-IL-2 plasmid complexes were int roduced into the nude mouse model of human osteosarcoma by direct int ratumor gene injection. Lactic dehydrogenase (LDH) assay was used to evaluate the activity of natural killer (NK) cells. Results 　Tf-PEI can effectively and specifically deliver murine interleukin-12 gene into human osteosarcoma. We also demonst rated that treatment using Tf-PEI-IL-12 plasmid complexes resulted in significant IL-12 expression in the tumor. Greater activity of NK was also observed in the therapy group as compared with the cont rols. Conclusion 　Tf-PEI is a high efficiency and low cytotoxicity tumor-targeted vector. It can successfully int roduce mIL-12 gene into nude mouse model of human osteosarcoma, and IL-12 gene therapy is able to induce the host antitumor immune response efficiently.