Background: T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses.This study examined whether the frequency of peripheral CD4+CXCR5+ TFH cells could be associated with HBV and HCV.Methods: The percentage of peripheral blood TFH cells in 23 immune-active (IA), 13 immune-tolerant(IT) CHB patients, 39 HCV, 12 spontaneously resolved HCV (SR-HCV) patients, and 12 healthy controls (HC) were characterized by flow cytometry analysis.Their serum HCV RNA, HBV, ALT and AST concentrations were measured.The potential association of the percentage of peripheral TFH cells with clinical measures was analyzed.In addition, the TFH ceils in HBV-transgenic mice was examined.Results: We found that the frequency of TFH in IA patients, SR-HCV and HCV patients were significantly higher than that of IT patients and HC.Furthermore, the percentages of ICOS+, PD-1+,and ICOS+PD-1+ in CD4+CXCR5+ TFH cells in CHB patients were significarntly higher than that of HC.In addition, treatment with adefovir dipivoxil for 12 weeks reduced the frequency of PD-1+ TFH cells and the concentrations of serum HBeAg and HBeAg, but increased the concentrations of serum HBeAb,HBeAb, IL-2 and IFN-γ in IA patients.Interestingly, a statistically significant negative correlation was found between the proportion of TFH cells and HCV RNA, but not with serum ALT and AST.Moreover, the frequency of splenic and liver TFH cells in HBV-transgenic mice was significantly higher than that of wild-type controls.Conclusions: These data indicate that TFH cells may participate in the HBV and HCV-related immune responses and that high frequency of TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.The humoral immune response stimulation by TFH could also take place in HCV, which is conducive to the treatment and prognosis of the disease.