Major histocompatibility complex (MHC) genes have been investigated because of their crucial role in the defense against pathogens and their high degree of polymorphism. We performed a case–control study to assess a genetic association of MHC genes with susceptibility to tuberculosis (TB). The allelic lineages HLA-A*02 and B*18 were significantly less frequent in TB patients (n = 112, 44.6% women) than in controls (n = 224, 51.5% women): 18.8% vs 26.5%; odds ratio (OR) = 0.64; P = 0.037 and 2.7% vs 6.9%; OR = 0.37; P = 0.041. The negative association with haplotype HLA-B*18-MICA*018 (2.3% patients vs 6.4% controls; OR = 0.34; P = 0.035) was significant as a consequence of strong linkage disequilibrium (D′ = 0.827 for patients and 0.923 for controls). These findings suggest a trend toward protection of the HLA-A*02 and HLA-B*18 alleles.