The etiology of lichen planus (LP) is still unknown and previous studies have found an association between LP and HLA-DR1, DR2, DR3, DR9 and DR10 in different populations. The aim of this study was to analyze the distribution of the HLA-DRB1 alleles in Mexican Mestizo patients with LP. The aim of this study was to determine the gene frequency of HLA-DR locus in Mexican Mestizo patients with LP. We studied 20 patients with LP and 99 healthy Mexican Mestizo controls. HLA-DRB1 was performed by PCR-SSO reverse dot blot hybridization. High resolution HLA typing was performed by PCR-SSP. The HLA-DRB1*0101 allele was associated significantly in LP patients compared with healthy controls (pC = 0.0007, OR = 5.46, 95% CI = 1.86-16.06). HLA-DRB1*0101 is a marker for the development of LP in Mexican Mestizo population, yet another gene or HLA marker within MHC region may be the causatively associated gene.