In conclusions, the present study demonstrated that EWS shRNA plasmid transfection and TFL treatment most effectively increased the anti-tumor mechanisms such as induction of differentiation and inhibition of angiogenesis as well as of invasion leading to apoptotic death in human Ewing’s sarcoma SK-N-MC and RD-ES cells in culture and animal models. The gene discussed is ZC3H12D; the disease is Ewing sarcoma.