SPOCK1 belongs to the SPARC family, which plays an important role in proliferation, invasion and migration of various tumour cells. However, the functions of SPOCK1 in osteosarcoma cell growth and proliferation have not been fully elucidated. In the present study, we found that SPOCK1 is significantly upregulated in osteosarcoma tissue. Moreover, overexpression of SPOCK1 was associated with tumour size, metastasis, Enneking stage and pathological degree. Furthermore, knockdown of SPOCK1 expression suppressed the growth of osteosarcoma cells in vitro and reduced tumourigenicity in nude mice in vivo. Additionally, our data suggest that inactivation of the mTOR-S6K signaling pathway participated in inhibition of SPOCK1-mediated suppression of osteosarcoma cell growth. These findings represent a novel pathogenetic mechanism of osteosarcoma development that provides a potential target for therapeutic strategies for osteosarcoma.