Interleukin 17F (IL-17F) is an inflammatory cytokine that plays an important role in autoimmune disease by inducing the expression of multiple chemokines, cytokines, and adhesion molecules. In vitro functional analysis revealed that IL-17F rs763780 polymorphism is associated with IL-17 expression and activity. Thus, considering the abnormal percentage of T helper 17 cells in patients with primary immune thrombocytopenia (ITP), we speculated there was a possible association between the IL-17F rs763780 polymorphisms and genetic susceptibility to ITP in a Chinese Han population. A total of 165 patients with ITP and 149 healthy controls were included in this study, and IL-17F rs763780 polymorphisms were analyzed by a polymerase chain reaction-restriction fragment length polymorphism system. The results showed that the frequency of the IL-17F rs763780 G allele in total patients with ITP or patients with chronic ITP was significantly lower than in normal controls (total ITP 3.6% vs controls 7.7%, P = .026; chronic ITP 3.5% vs controls 7.7%, P = .031). However, no significant difference in genotype frequencies was found among total patients with ITP, patients with chronic ITP, and normal controls. We further analyzed the association of IL-17F polymorphisms with clinical parameters of patients with ITP, and no association revealed between gene distribution and first onset age, clinical therapy response to glucocorticoids, or disease course. What's more, an evident discrepancy with allelic frequencies was observed between female patients with ITP and gender-matched controls. In conclusion, IL-17F rs763780 polymorphisms may be associated with the development of ITP in a Chinese Han population.