〔Abstract〕 Objective To investigate the mechanism of down-regulation of the phosphatase and tensin homolog deleted on chromosome ten(PTEN) caused by hepatitis B virus(HBV) infection and the antiviral activity of interferon α(IFN-α). Methods HepG2 cells and HepG2.2.15 cells were cultured under suitable conditions. HepG2 cells were transfected with empty vector(pcDNA3.1) and HBV1.3 plasmid respectively, and the protein expression of PTEN was detected by Western blot; pcDNA3.1 and PTEN over-expression(PTEN-OE) plasmid were transfected into HepG2.2.15 cells respectively. Chemiluminescence was used to analyze the expression of HBV-related antigens in the cell culture supernatant, and real-time quantitative PCR(qRT-PCR) was used to analyze the expression of HBV pregenomic RNA(HBV pgRNA); the synthetic RNA duplex [poly(I∶C)]was used to stimulate PTEN-OE cells, qRT-PCR was used to analyze IFN-α mRNA expression and Western blot was used to analyze the expression of interferon regulatory factor 9(IRF9) protein as well as myxovirus resistance protein 1(MxA) protein in the JAK/STAT signaling pathway.Results In HepG2 cells expressing HBV transiently and HepG2.2.15 cells stably expressing HBV, the expression of PTEN protein both decreased; the expression of HBV-related antigens and HBV pgRNA decreased in PTEN-OE HepG2.2.15 cells compared with the control group. After the treatment by poly(I∶C), the level of IFN-α mRNA was significantly higher than that of the control group, and the expression of IRF9 and MxA ptotein related to the JAK/STAT signaling pathway both increased.Conclusion HBV may play a role in antagonizing the antiviral activity of IFN-α by down-regulating the expression of PTEN.