Introduction: HLA-DRB1 alleles were derived from MHC class II molecules. These alleles encoded sIgA secretion which contribute as a barrier to S. mutans colonization. HLA-DRB1 was known as genes with high mutations causing differences in peptide bond, thus affecting the progression and vulnerability to a disease. The purpose of this study was to determine the effect of mutations in HLA-DRB1 alleles in different dental caries risk. Methods: In this study, we extracted the genomic DNA from whole blood samples of 30 patients with low level dental caries (indeks def-t < 2) as control group and high level dental caries (deft > 3) as case group. HLA-DRB1 varians were studied through genomic DNA isolation for PCR-RFLP. RFLP is analyzed through BseRI, BsaJI, RsaI, and Sau961 restriction enzymes was used in this assay. Results: The PCR-RFLP typing method was evaluated on 60 genomic DNA samples, result found that all samples were divided into 5 groups of variants, two variants in the control group and three variants in the case group. Conclusion: PCR-RFLP was shown to be a sensitive method for the detection of mutation in HLADRB1 alleles caused a dental caries level differences. HLA-DRB mutations caused changes in signal transduction and therefore contributes to imunogenetik pathway of dental caries.