These metal-doped composites presented exceptional anti-tumor effects in human osteosarcoma cells (HOS) through improved cellular internalization efficacy and free radical generation, respectively/confirmed Fenton-like reaction-induced chemodynamic therapy (CDT), over-expressed hypoxia-inducible factor (HIF)-1α through p53 pathway, and formation of calcified nodules. This evidence concerns the gene HIF1A and osteosarcoma.