Pulmonary tuberculosis (TB) is a socially significant disease and a global challenge faced by public health. The NF-kB signaling pathway is involved in differential expression of the genes involved in immune responses and regulation of inflammation in response to infection. The study aimed to assess associations of the NFKB1 allelic variants with TB based on the panel of SNPs (rs4648050, rs4648051, rs4648055, rs4648058, rs4648068, rs1609993) located within the NF-kB1 р105→р50 processing region. Total DNA was extracted from blood samples (phenol-chloroform extraction) of patients with TB (n = 93) and the population control group (n = 96) consisting of residents of the Kemerovo Region. Genotyping was performed by real-time PCR, and the results were processed using the resources of the Statictica, SNPStats, Arlequin software packages. Ethnic features (p < 0.05) of the Russian population of Siberia (population control group) were demonstrated based on the rs4648050 and rs4648051 allele frequencies. Differences (p < 0.05) of the genetic profile of the sample of patients with pulmonary tuberculosis throughout the entire SNP complex, except for rs1609993, were noted. We showed differences (p < 0.05) in the rs4648068 allelic frequencies between the population control sample and patients with pulmonary tuberculosis. The association with susceptibility to pulmonary tuberculosis was determined for genotypes АА*rs4648055 (OR = 2.51; p = 0.05) and GG*rs4648068 (OR = 2.16; p = 0.03). The findings are indirect evidence of modifying effects of the SNP located within the processing zone in the gene NFKB1 and its possible contribution to the NF-kB1 р105/р50 protein balance and immune response to mycobacterial infection.