Cell division is closely related to telomerase activity (hTERT mRNA). Lower expression of lymphocitic hTERT mRNA may easily cause cell aging, which is not beneficial to maintaining a durable lymphocyte division. To date, there is no study to investigate IFN alpha therapy on hTERT mRNA expression in PBMCs of patients with chronic hepatitis B (CHB). We quantitatively detected hTERT mRNA from study subjects and made each hTERT mRNA normalized (NhTERT mRNA). Mean NhTERT mRNA level was lower in either CHB group, but it significantly increased in IFN alpha-treated group compared with CHB control group, and a longer duration of IFN alpha therapy could increase the level. Moreover, the mean NhTERT mRNA in subgroup with HBeAg loss was significantly higher than that in subgroup without. NhTERT mRNA was markedly correlated with CD3(+) T lymphocyte count and CD4(+)/CD8(+) ratio. The results showed that IFN alpha therapy could upregulate the expression of hTERT mRNA in PBMCs.