Emerging pieces of evidence indicate that microRNA-466 (miR-466) serves as a tumor suppressor in several human tumors, including colorectal cancer and prostate cancer. However, whether miR-466 is involved in osteosarcoma (OS) progression remains largely unknown. The present study demonstrated that miR-466 was significantly downregulated in OS tissues and cell lines. Furthermore, it was revealed that the expression of miR-466 was negatively correlated with OS severity. Moreover, low miR-466 expression in patients with OS predicted poor prognosis. Through functional experiments, miR-466 overexpression significantly inhibited the proliferation and cell cycle of OS cells while inducing cellular apoptosis. In terms of mechanism, it was revealed that CCND1 was a target of miR-466 in OS cells. miR-466 overexpression suppressed CCND1 expression in OS cells. A reverse association was observed between the expression levels of miR-466 and CCND1 in OS tissues. Furthermore, CCND1 restoration in OS cells significantly rescued the effects of miR-466 on cellular proliferation and apoptosis. Overall, the results of the present study demonstrated that miR-466 suppressed OS progression by targeting CCND1, suggesting that miR-466 may be a promising biomarker and therapeutic target for OS prognosis and treatment.