The present study is the first to confirm that silencing of APE1 by adenoviral vector Ad5/F35-mediated APE1 siRNA enhanced sensitivity of human HCC cells to radiotherapy in vitro and in vivo. Therefore, inhibition of APE1 protein by APE1-specific siRNA may be a strategy to overcome radioresistance and then improve its therapeutic efficacy for hepatoma. Here, APEX1 is linked to hepatocellular carcinoma.