Abstract: Objective To investigate the expression and role of follicular helper T cells ( Tfh) in children with hand, foot and mouth disease ( HFMD) caused by coxsackievirus A6. Methods Thirty-three patients with HFMD caused by coxsackievirus A6 and 26 healthy controls ( HC) from Hangzhou Children's Hospital during June 2022 and August 2023 were enolled in this study. Their whole blood and serum samples were ollected. Flow cytometry was used to determine the proportion of Th cells in peripheral blood. Then,the proportions and correlations of Th cells between HFMD patients and HC were analyzed. Results The proportions of CXCR5*CD4*T ellls in CD4* T cells in the HFMD and HC groups were 3.95(2.31, 6.21)% and 1.44(0.94, 2.43) %, respectively, and there was significant difference between them ( P<0.001). The proportions of ICOS+ CXCR5* CD4* Tfh cells and PD-1*CXCR5+ CD4* Tfh cells in .the HFMD group (1.44[0.81, 2.86]% and 1.64[0.65, 4.05]%) were also significantly higher than those in the HC group ( 0.84[0.27, 1.46]% and 0.47[0.13, 1.12]%， P<0.05). Moreover, a positive correlation was found between the CXCR5* CD4* Tfh cells and the expressions of ICOS* and PD-1*( P<0.05). Conclusion Tfh cells may play an important role in the immune response of children with HFMD caused by coxsackievirus A6.