Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1α in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1α in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions. In addition, HIF-1α was downregulated via lentiviral vector‑mediated RNA interference (RNAi) in the MG-63 human osteosarcoma cell line. The results revealed that HIF-1α was negatively correlated with IDH-1 in the osteosarcoma tissues. Both in MG-63 and 143B cell lines, the expression of HIF-1α was increased while IDH-1 was decreased under a hypoxic condition compared to normal conditions. HIF-1α downregulation promoted IDH-1 expression in the MG-63 cell line under either normal or hypoxic conditions. In conclusion, our findings suggest that HIF-1α inhibits IDH-1 in osteosarcoma and consequently increases the incidence of osteosarcoma.