Knockout of FOXO3a maintained the cell viability of sorafenib-treated 4 HCC cells in a quiet low level no matter in normoxia or in hypoxia, and showed the similar capacity to enhance the cytotoxicity of sorafenib on HCC cells cultured in hypoxia compared to those in normoxia (Fig. 5A). This evidence concerns the gene FOXO3 and hepatocellular carcinoma.