Background: Recurrent Aphthous Stomatitis (RAS) is a common oral inflammatory disease with unknown pathogenesis. Although the immune system alterations could be involved in predisposition of individuals to oral candidiasis, precise ethiologies of RAS have not been understood yet. Considering the inflammatory nature of interleukin (IL) -17F and RAS, we aimed to sequence the gene in a number of patients with RAS to identify any disease-associated mutation.Methods: Sixty-two Iranian patients with RAS and fifty healthy subjects enrolled in this study. After DNA extraction from the whole blood, amplification was accomplished by polymerase chain reaction for IL-17F.Finding: The results of sequencing revealed a missense, heterozygous mutation, converting a threonine to proline in a patient with RAS. The Polyphen software suggested a damaging probability predicting this substitution to have a harmful effect on IL-17F protein function. Nevertheless, this substitution was predicted to change the β-aggregation propensity using TANGO software. Such mutation was not detected in any control subject. In addition, one of the IL-17F SNPs is associated with the RAS.Conclusion: This is a first study showing a mutation that seems to be associated with susceptibility to RAS. Further studies on more patients with RAS are required to confirm this finding.