Long non-coding RNAs (lncRNAs) play a key role in regulating tumor growth and metastasis of osteosarcoma (OS). Recent studies have reported that lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in OS tissues and contributes to the proliferation, migration and invasion of OS cells. However, the molecular mechanism involved in the oncogenic role of SNHG16 in OS remains poorly known. In the current study, we confirmed that SNHG16 expression was markedly up-regulated in OS tissues compared to paracancerous tissues. The elevated level of SNHG16 closely associated with advanced tumor stages, larger tumor size and more distance metastasis. Furthermore, OS patients with high SNHG16 level had a significant poorer overall survival compared to patients with low SNHG16 level. Knockdown of SNHG16 suppressed the proliferation, migration and invasion of U2OS and MG63 cells. Mechanistically, SNHG16 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-1301 and inversely regulated its abundance in OS cells. Notably, suppression of miR-1301 rescued SNHG16 knockdown attenuated OS cell proliferation, migration and invasion. SNHG16 knockdown reduced the expression of BCL9 protein in OS cells. Accordingly, BCL9 restoration facilitated the proliferation, migration and invasion of OS cells with SNHG16 knockdown. Collectively, these results suggest that SNHG16 is a potential prognostic biomarker for OS patients. SNHG16 promotes BCL9 expression by sponging miR-1301 to facilitate the proliferation, migration and invasion of OS cells.