As one of the blood-rich malignancies, the growth and metastasis of osteosarcoma both depend on its angiogenesis, a procedure in which vascular endothelial growth factor (VEGF) acts essentially. Although with the advent of neoadjuvant chemotherapy, more aggressive surgical excision and logical therapy strategy, the 5-year survival rate remains relatively stable at 70%, at best. However, antiangiogenic therapeutics, through gene silencing and targeting key sequences, probably brings an outlook to the conventional algorithm. In our current research, human-specific VEGF-siRNA (small interfering RNA) mediated by adenovirus was constructed and a cell line of MG63 was cultured and used to make an osteosarcoma-bearing nude mice model. The recombined adenovirus vector of Ad-VEGF-siRNA could successfully suppress VEGF expression and slow down the multiplication of MG63 cells in vivo; likewise, the down regulation of VEGF could be detected in vitro of the animal model. Inhibitory effects on osteosarcoma growth and blockage of pulmonary metastasis could be observed in the following oncotherapy procedure. The study demonstrates potent growth and pulmonary metastasis inhibitory effects of VEGF-siRNA on osteosarcoma in vivo and in vitro, which could potentially be applicable to the treatment of cancers as an antiangiogenic therapeutic in the near future.