Suppressor of variegation 3‑9 homologue 2 (SUV39H2), a SET domain‑containing histone methyl-transferase, trimethylates histone H3 at lysine 9 and serves crucial roles in heterochromatin organization and genome stability. SUV39H2 is overexpressed in various types of human cancer, whereas it is almost undetectable in normal adult tissues, except testis. The aim of this study was to investigate a potential role of SUV39H2 in osteosarcoma. In the present study, increased SUV39H2 expression levels were observed in osteosarcoma, the most common primary bone cancer in children and adolescents, and the knockdown of SUV39H2 expression by specific small interfering RNAs in osteosarcoma cells markedly suppressed cancer cell growth and led to a notable reduction in cell viability. Furthermore, overexpression of SUV39H2 promoted cell proliferation, which indicated that SUV39H2 may possess oncogenic activity in human osteosarcoma. Notably, depletion of SUV39H2 expression caused an increase in the population of G1 phase and induced apoptosis, which implied that SUV39H2 may have biological significance in the process of cell cycle. These results indicated that SUV39H2 may be an ideal target for osteosarcoma therapeutics.