In this report, we showed that Licochalcone A treatment induced cleaved-caspase 8 and caspase 3, but decreased the levels of Bax and cleaved-caspase 9, indicating that Licochalcone A triggers apoptosis that mediated by the extrinsic pathways in osteosarcoma cell lines. Here, CASP8 is linked to osteosarcoma.