Osteosarcoma is a bone malignancy characterized by strong invasiveness and rapid disease progression. The tumor microenvironment of osteosarcoma contains various types of immune cells, including myeloid-derived suppressor cells, macrophages, T cells, and B cells. Imbalances of these immune cells can promote the proliferation and metastasis of osteosarcoma. Recent studies have indicated a substantial increase in the levels of myeloid-derived suppressor cells, an immune cell associated with immunosuppressive and pro-cancer effects, in the peripheral blood of patients with osteosarcoma. Moreover, the levels of the pro-inflammatory cytokine interleukin 18 are positively correlated with those of myeloid-derived suppressor cells in the peripheral blood of animal models of osteosarcoma. In this review, we explore the function of myeloid-derived suppressor cells in osteosarcoma based on the clinical diagnoses of patients with osteosarcoma and discuss future therapeutic approaches for targeting osteosarcoma. Targeting myeloid-derived suppressor cells represents a promising approach to improving the prognosis and survival rates of patients with osteosarcoma.