BACKGROUND: Chronic hepatitis B (CHB) is one of?the major infectious diseases in which?CD4+ T helper (Th) cells play a crucial role. Th9 cells are a distinct subset of CD4+ Th cells with important physiological functions. OBJECTIVE: The study aimed to assess the potential involvement of Th9 cells in the?inadequate immune response leading to chronic HBV infection. PATIENTS AND METHODS: Peripheral blood samples were collected from 22 CHB patients and 16 healthy controls (HC). The frequencies of circulating Th9, Tc9, Th1, and Tc1 cells were determined by flow cytometry. Serum levels of IL-9 and IL-10 were analyzed by ELISA. Serum biochemical indices of liver function were measured using an automated analyzers. Serum HBV DNA loads were analyzed by real-time PCR. The potential association of the frequency of Th9, Tc9, Th1 or Tc1 cells with clinical parameters was assessed. RESULTS: The frequency of circulating Th9 cells was significantly lower in CHB patients than those in HC. However, no significant differences in the frequency of Tc9, Th1 or Tc1 cells were observed between the two groups. The percentages of Th9 cells, but not Tc9 cells, were negatively correlated with HBV DNA loads, whereas the percentages of Tc1 cells were positively correlated with viral loads in CHB patients. Moreover, there was a positive correlation between serum levels of IL-9 and IL-10 and HBV DNA loads in patients with chronic HBV infection. CONCLUSION: The depletion of Th9 cells is associated with the development of chronic HBV infection.