Objective       To investigate the candidate molecular markers for predicting the efficacy of sorafenib in treatment of advanced hepatocellular carcinoma (HCC).       Methods       Clinical data of 54 patients with identified advanced HCC and receiving sorafenib treatment who hospitalized in the First Affiliated Hospital of Sun Yat-Sen University from December 2008 to October 2011 were collected and analyzed in this study. Their liver tissue sections from the paraffin-embedded liver tumor biopsies before sorafenib treatment were analyzed with immunohistochemical staining (IHC) for phosphorylated extracellular signal regulated kinase (pERK)

vascular endothelial growth factor receptor (VEGFR)

p70 S6 kinase (Ps6k) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). According to the results of IHC

the patients were divided into high- and low-expression subgroups

and then analyzed with the time to progression (TTP) of the cohort in order to investigate the molecular markers for predicting the efficacy of sorafenib.       Results       The TTP was significantly longer in the patients with higher expression of VEGFR and pERK than those with lower expression (P0.05). But there was no difference in the TTP between the patients with high and low expression of Ps6k (P0.05). No positive expression of PTEN was seen in the cohort.       Conclusion       In the treatment of advanced HCC

sorafenib will cause longer TTP in the patients with high expression levels of VEGFR and pERK. VEGFR and pERK maybe the candidates as molecular markers for sorafenib in treating advanced HCC.