Long non‑coding RNA (lncRNA) NR2F1 antisense RNA 1 (NR2F1‑AS1) has been reported to be an oncogene in several cancer types, including osteosarcoma (OS). However, the underlying fundamental molecular mechanism of NR2F1‑AS1 in OS remains largely unknown, which the present study aimed to elucidate. The present study demonstrated that NR2F1‑AS1 expression is markedly increased in OS, and NR2F1‑AS1 was shown to exert oncogenic functions in OS. Further molecular mechanistic studies revealed that microRNA (miR)‑485‑5p and miR‑218‑5p were direct targets of NR2F1‑AS1. More importantly, miR‑485‑5p and miR‑218‑5p exhibited low expression levels and were negatively correlated with NR2F1‑AS1 expression in OS tissues. It was then identified that baculoviral inhibitor of apoptosis repeat‑containing 5 (BIRC5) was a direct target of miR‑485‑5p and miR‑218‑5p in OS cells. Furthermore, a series of experiments suggested that NR2F1‑AS1 affects the proliferation, migration, invasion and apoptosis of OS cells by regulating BIRC5. Finally, it was revealed that silencing of NR2F1‑AS1 repressed the OS cell malignant phenotype by binding with miR‑485‑5p and miR‑218‑5p, and then downregulating BIRC5 expression, which suggests that the NR2F1‑AS1/miR‑485‑5p/miR‑218‑5p/BIRC5 axis could be a potential target for treating OS.