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Recurrent aphthous stomatitis (RAS) is a common painful, ulcerative oral inflammatory disorder with unknown etiology. Immune system through inflammation process plays a role in outbreaks of RAS ulcers. Interleukin-1 (IL-1) and IL-6 are the most potent proinflammatory cytokines. Single nucleotide polymorphisms (SNPs) of IL-1 and IL-6 genes can affect the secretion of these cytokines. The aim of this study was to investigate the association between RAS and IL-6 and IL-1 in subjects with RAS. Genomic DNA was obtained from 60 Iranian patients with RAS. IL-1a C-889 T, IL-1 b C-511 T, IL-1 b C+ 3962 T, IL-1R C pst-I 1970 T, IL-1Ra C Mspa-I11100 T, IL-6 C-174 G and IL-6 A nt+ 565 G polymorphisms were determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). The frequency of C-174 C genotype in the patients group was significantly different from the healthy control. No other significant difference was found in genotype and alleles frequencies between the two groups. These results indicate that certain SNPs of IL-6 gene at position-174 which located in promoter have association with predisposition of individuals to RAS.