BACKGROUND: CD4(+) T-helper cell is crucial for the inflammatory autoimmune condition of oral lichen planus (OLP). Recently, the pathogenetic functions of T follicular helper (Tfh) cells, a subtype of CD4(+) T-helper cells, have been revealed in autoimmune diseases for their pivotal regulation on humoral immunity. To explore the potential pathophysiological role of Tfh cells in OLP, the expression of circulating Tfh-like cells and its correlations with IL-21 and B cells were investigated. METHODS: The frequencies of CXCR5(+) CD4(+) Tfh-like cells and CD19(+) B cells were analyzed in peripheral blood of patients with OLP and controls by flow cytometry, respectively. Besides, the serum IL-21 concentration was measured using ELISA technology. Furthermore, the correlations of CXCR5(+) CD4(+) Tfh-like cells with CD19(+) B cells and serum IL-21 expression levels were evaluated. RESULTS: This study showed significant increased circulating Tfh-like cells (P < 0.05) and B cells (P < 0.0001), as well as decreased serum IL-21 expression (P < 0.001) in OLP. Besides, the frequency of Tfh-like cells exhibited negative correlation with B cells in OLP (r = -0.435, P < 0.05). In particular, the proportion of CXCR5(+) CD4(+) Tfh-like cells in peripheral blood mononuclear cells of erosive OLP was higher than non-erosive OLP and controls (P = 0.012 and 0.021, respectively). CONCLUSIONS: Increased circulating Tfh-like cells may be involved in the pathogenesis of OLP through abnormal modulation on B-cell proliferation and IL-21 production, and associated with different clinical forms of OLP.