T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1)(+) Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1(+) Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1(+), PD-1(+)CD154(+), and PD-1(+) interleukin (IL)-21(+) Tfh cells, and CD38(+)CD19(+) and CD38(+)CD19(+)CD40(+) B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-gamma were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0.05). However, no significant difference was found in PD-1(+)BCL-6(+) or PD-1(+)ICOS(+) Tfh cells. Furthermore, the percentages of PD-1(+) Tth and PD-1+CD154+ Tfh cells were negatively correlated with the estimated glomerular filtration rate (eGFR), but positively correlated with the 24-h urinary protein concentration and serum IL-21 level. The percentages of PD-1(+) Tfh and PD-1(+)CD154(+) Tfh cells were positively correlated with the percentages of CD38(+) plasma cells and active CD38(+)CD40(+) plasma cells, respectively. After an 8-12-week treatment with prednisolone, the percentages of PD-1(+), PD-1(+)CD154(+), and PD-1(+)IL-21(+) Till cells as well as the serum level of IL 21 were significantly reduced; in contrast, the serum levels of IL-4 and IL-10 were increased (P < 0.05). We conclude that increased PD-1(+)CD154(+) Tfh cells are possibly the most important functional subset of PD-1(+) Tfh cells and may contribute towards the pathogenesis of MCD.