Osteosarcoma is the most common type of human primary malignant bone tumor with a potential propensity for local invasion and distant metastasis. Thus, this study focused on the expression and roles of IRX2 in the development of osteosarcoma. The mRNA expression levels of IRX2 in tissue samples of 69 cases of human osteosarcoma were detected by a quantitative polymerase chain reaction assay. The associations between the expression levels of IRX2 and the pathological features of the tumor tissues were analyzed. Functional studies were performed by MTT and Matrigel invasion assays following IRX2 knockdown with a lentivirus vector. Western blotting was used to assay the protein expression levels of IRX2, p‑AKT and matrix metalloproteinases (MMP). The results revealed that the expression levels of IRX2 were significantly increased in the primary human osteosarcoma tissues compared with those in the normal tissues, and the increase was significantly correlated with the tumor progression and prognosis of the patients. Furthermore, the proliferation and invasion of the cells were suppressed following IRX2 knockdown. Additionally, the mechanism by which IRX2 promoted cell proliferation and invasion by activating AKT and MMP9 was detected. In conclusion, these results indicated that IRX2 promotes proliferation and invasion in osteosarcoma and implicated the potential of IRX2 in cancer therapy.