Chen and co-workers have demonstrated that prolonged sorafenib treatment heightens tumor hypoxia, and increases expressions of CXCR4 and SDF-1α in HCC [21, 22], which indicates that down-regulation of CXCR4 level or intervention of SDF-1/CXCR4 signaling pathway may overcome sorafenib resistance and evasion [23]. Here, CXCR4 is linked to hepatocellular carcinoma.