OBJECTIVE: To explore the possible relationship between recurrent aphthous ulcer (RAU) and single nucleotide polymorphism (SNP) of transforming growth factor-β1 (TGF-β1)-509T/C and interleukin-10 (IL-10)-1082A/G sites. METHODS: A total of 138 RAU patients were recruited for this study. The control group consisted of 124 subjects. TGF-β1-509T/C and IL-10-1082A/G sites were detected by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) and sequence specific primer-polymerase chain reaction (SSP-PCR). Relative risk ratios were estimated by odds ratios (OR) and 95% confidence interval (95%CI). RESULTS: Significant differences were found in the genotype frequencies or allele frequencies of TGF-β1-509T/C and IL-10-1082A/G sites between the RAU patients and controls (P < 0.05). CT genotype (OR = 1.231, 95% CI = 0.702-2.160), TT genotype (OR = 2.482, 95% CI = 1.250-4.927), and T allele (OR = 1.465, 95% CI = 1.036-2.074) at the TGF-β1-509 site exhibited high risks. AG genotype (OR = 1.391, 95% CI = 0.808-2.396), GG genotype (OR = 4.165, 95% CI = 1.944-8.924), and G allele (OR = 2.134, 95% CI = 1.474-3.089) at the IL-10-1082A/G site also showed high risks. CONCLUSION: TGF-β1-509T/C and IL-10-1082A/G sites are associated with the risk of RAU. The TGF-β1 gene-509T allele and IL-10 gene-1082G allele may serve as genetic determinants for RAU.