As a part of our ongoing effort for the identification of natural products with anti-cancer effects in vitro and in vivo, we present here first time that 4-MD inhibits the growth and induces apoptosis of osteosarcoma cells through the suppression of the JAK2/STAT3 pathway, and inhibits growth of osteosarcoma cells in a xenograft mouse model. This evidence concerns the gene STAT3 and osteosarcoma.