Abstract: Objective To investigate the influence of sodium phenyl butyrate (SPB) on the apoptosis, expressions of HBeAg and HBeAg and HBV-DNA content of HepG2.2.15 cells. Methods The MTT assay was used to determine the cell proliferation at 24, 48h with different concentrations（1.0, 2.0, 4.0, 8.0μmol／L） of SPB. The flow cytometry（FCM）was employed to measure the cell cycle and cell apoptosis at 24， 48h with 2.0，4.0μmol/L SPB. The expressions of HBsAg and HBeAg and HBV-DNA content in supernatants at 72h with 8.0μmol/L SPB were measured by chemiluminescence detection and RT-PCR. Results Treatment with SPB could increase the proliferation inhibition rate at a time and dose dependent manner（P＜0.05）. The early and late apoptosis rates and the percentage of cells in G0/G1 phase were higher，but the percentage of cells in S phase were lower in SPB group than control group（P＜0.05）. The apoptosis rate was higher at 48h than 24h under the same concentration of SPB（P＜0.05）.The expressions of HBsAg, HBeAg and HBV-DNA levels were 40.22±1.57，69.46±1.75 and 9.34±0.54 after 72h treatment with 8.0μmol/L SPB，higher than 18.33±0.58，34.92±1.26 and 5.52±0.45（P＜0.05）in the control group. Conclusion SPB could induce differentiation and promote the apoptosis of HepG2.2.15 cells. SPB could stimulate HBV replication，so it may not be suitable to treat hepatocellular cancer patients with HBV infection.