OBJECTIVE: Osteosarcoma can form tumor osteoid tissue and bone tissue directly or indirectly through cartilage stage. It mainly occurs in children and adolescents with high mortality. MicroRNA (miRNA) possesses tissue sensitivity as tumor biomarker and plays a promoting or inhibitory role in tumor pathogenesis as oncogene or tumor suppressor gene. It was found that miR-155 was abnormally expressed in tumor and could be treated as a biomarker for cancer progression. However, miR-155 expression in osteosarcoma and related mechanism still remains unclear. This study aimed to explore the role of miR-155 in osteosarcoma occurrence and development. MATERIALS AND METHODS: Osteosarcoma cell line MG-63 was cultured in vitro and transfected by miR-155 mimics or inhibitor. MiR-155 expression was examined by Real-time PCR (RT-PCR). Cell proliferation was evaluated by MTT assay. Caspase 3 activity was determined by caspase 3 activity detection kit. Cell invasion was measured by transwell assay. B-cell lymphoma-2 (Bcl-2) and nuclear factor kappa B (NF-kappa B) protein expressions were assessed by Western blot. RESULTS: MiR-155 mimics significantly up-regulated miR-155 expression, promoted MG-63 cell proliferation and invasion, inhibited caspase 3 activity, and up-regulated expressions of NF-kappa B and Bcl-2 compared with control group (p < 0.05). However, miR-155 inhibitor significantly inhibited MG-63 cell proliferation and invasion, enhanced caspase 3 activity, and reduced expressions of NF-kappa B and Bcl-2 compared with control group (p < 0.05). CONCLUSIONS: MiR-155 affected osteosarcoma cell proliferation and apoptosis through regulating NF-kappa B signaling pathway, indicating it might be a new biomarker for osteosarcoma diagnosis and treatment.