Background: Oral lichen planus (OLP) is a common autoimmune inflammatory disorder that is difficult to cure, and its pathogenesis is still unknown. The major histocompatibility complex (MHC) class II transactivator (CIITA) gene has been reported to be an important candidate in some classical autoimmune diseases, and certain single nucleotide polymorphisms (SNPs) in CIITA gene have been confirmed to be associated with susceptibility to some autoimmune diseases. This research was conducted to investigate the existence of any correlation between OLP and SNPs (rs4774, rs6498122) in CIITA gene separately and in combination method by using (buccal swabs and blood sample), and to compare their existence with that of apparently healthy group. The validity of DNA extraction method from buccal swabs as convenient, painless, less risk of diseases transition and cost-effective alternatives way to blood sampling for participants and researchers was also assessed in this study. Materials and Methods: A case-control study was performed to genotype detection of 2 SNPs in the CIITA gene from buccal swab and blood sample from OLP patients as patient group, and buccal swab and blood sample from healthy people as control group; this was carried out by qRT-PCR. Results: The SNP rs4774 variant in exon 11 (G/C, Gly500Ala) of CIITA gene is significantly associated with OLP in heterozygous frequency, SNP rs6498122 variant in intron 5 (A/G) of CIITA gene is significantly associated with OLP in mutant frequency, and at allele frequency the two SNPs is significant. When the two SNPs analyzed in genotypes combination method for SNPs (rs4774, rs6498122) between healthy and OLP patient groups, significant result was shown when the rs4774/rs6498122 be wild/mutant and hetero/hetero. Also, the result of DNA extraction for SNPs analyses of buccal swab is the same of blood sample. Conclusion: Data was shown that the two SNPs rs4774 and rs6498122 at CIITA gene are associated with OLP and could also indicate the autoimmune characteristics of OLP. Buccal swab instead of blood sample in SNPs genetic research can be used.