Cytokines have an important role in the pathogenesis and disease progression on oral lichen planus (OLP). The aim of this study is to investigate the impact of gene polymorphisms of T-helper cell subtype Th1/Th2 cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) on OLP in a Chinese cohort with Han ethnicity. Three single-nucleotide polymorphisms (SNPs) of the IL-10 gene (IL-10) at positions -1082G/A, -819C/T, and -592C/A and one SNP of the TNF-alpha gene (TNFG) at position -308G/A were analyzed in 151 patients with OLP and 143 healthy controls using polymerase chain reaction with sequence-specific primers (PCR-SSP) method and polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The data revealed that there was no difference between the OLP patients and healthy control groups in frequencies of both TNF-alpha and IL-10 alleles (P = 0.053) and genotypes (P = 0.197). However, the frequencies of TNF-alpha-308A allele (P = 0.013) in patients with erosive OLP were significantly greater than the corresponding values in the control group. Using PHASE software, four haplotypes were deduced from the three IL-10 polymorphisms -1082 G/A, -819 C/T, and -592 C/A, named haplotypes I to IV. The haplotypes IV, which correlated with a lower serum level of IL-10, has a significant association with OLP (P = 0.008). Our study suggests that TNF-alpha and IL-10 gene polymorphisms seem to have some influence on the disease susceptibility and progression of OLP in this Chinese cohort with Han ethnicity.