Although some conditions or pathways leading to sorafenib resistance, including AKT activation, hypoxic environment, Epithelial–mesenchymal transition (EMT), cancer stem cells/tumor-initiating cells, Epidermal growth factor receptor (EGFR) activation, c-Jun activation and autophagy have been reported (7), more efforts should be input to further elucidate the complicated sorafenib resistance mechanism and improve the outcome of sorafenib treatment in HCC patients. The gene discussed is EGFR; the disease is cancer.