To investigate the effect of ganoderic acid A (GA-A) on the biological behaviors of human osteosarcoma cells in vitro.MG63 and HOS cells were treated with 0.1, 0.25, and 0.5 mmol/L GA-A, and the changes in cell proliferation, apoptosis and migration were evaluated using MTT assay, flow cytometry, and Transwell assay, respectively. The expressions of STAT3, p38, and NF-κB1 in the cells were analyzed by Western blotting.GA-A effectively inhibited the proliferation of human osteosarcoma HOS and MG-63 cells in a dose-dependent manner, and induced obvious cell apoptosis in both cells. Treatment with 0.5 mmol/L GA-A also resulted in significant inhibition of the invasion of both cells. The results of Western blotting showed that GA-A down-regulated the expression level of phosphorylated STAT3 and increased the phosphorylation level of p38 and NF-κB1 expression in both cells.GA-A can induce proliferation inhibition, apoptosis and suppression of invasion in human osteosarcoma HOS and MG-63 cells.