In the present study, we showed that IL-6 treatment rescued the anti-proliferation effect of diosmetin and immunoprecipitation also showed STAT3 dimerization (activation) was significantly suppressed by diosmetin, indicating the involvement of STAT3 activation (phosphorylation and dimerization) in cell proliferation and apoptosis of osteosarcoma cells, and blockade of the STAT3 pathway may be a therapeutic strategy against osteosarcoma. The gene discussed is IL6; the disease is osteosarcoma.