Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. There are some studies in the literature demonstrating association between cytokines genes polymorphisms and susceptibility to develop some immune-mediate conditions. The purpose of this study was to investigate cytokine gene polymorphisms in a sample of Brazilian patients with OLP. Fifty-three patients with OLP (mean age = 43.1 years; range 20-68 years) and 53 healthy volunteers (mean age = 42.9 years; range 21-67) were genotyped for IL-1beta +3954 (C/T), IL-6-174 (G/C), IL-10-1082 (G/A) and TNFA-308 (G/A) gene polymorphisms. Statistical analysis was based on the use of logistic regression (P-values below 0.05 were considered as significant). IL-6 and TNFA homozygous genotypes were significantly more often detected in OLP patients. These genotypes were associated with an increased risk of OLP development (OR 6.89 and 13.04, respectively). IL-1beta and IL-10 gene polymorphisms were not related to OLP development. Our findings clearly demonstrate an association between inheritance of IL-6 and TNFA gene polymorphisms and OLP occurrence, thus giving additional support for genetic basis of this disease.