This study was aimed to investigate the effect of rhIL-6 and rhEPO on hepcidin mRNA expression in HepG2 cells and human primary hepatocytes, and mechanism of rhEPO in treatment of anemia of chronic disease (ACD). The HepG2 cells and human primary hepatocytes were cultured with medium containing different concentrations of rhIL-6 and rhEPO for a certain time, then mRNA was isolated and its RT-PCR was performed, the bands were photographed and analyzed by UVI band, the hepcidin and G3PDH mRNA ratio were semi-quantitatively analyzed. The expression levels of hepcidin in GepG2 cells and human primary hepatocytes at different conditions were compared. The results showed that the hepcidin mRNA expression in HepG2 cells and human primary hepatocytes could be enhanced by rhIL-6, the rhEPO could inhibit rhIL6-induced hepcidin mRAN expression. The rhEPO alone basically did not influence hepcidin mRNA expression in HepG2 cells. It is concluded that Hepcidin mRNA expression in HepG2 cells and human primary hepatocytes can be elevated by rhIL-6 with concentration- and time-dependent manner in certain range. rhEPO can inhibit this effect of rhIL-6.