Objective To explore the correlation between single nucleotide polymorphisms(SNPs) of high-mobility group box 1 protein (HMGB1) and susceptibility of pulmonary tuberculosis(PTB) patients in northern Henan. Methods 320 patients who were diagnosed with PTB in the First Affiliated Hospital of Xinxiang Medical University from January to December 2017 were selected as the tuberculosis group, and 300 healthy people who underwent physical examination during the same period were selected as the control group. Genotyping of HMGB1 rs1412125(-1615A/G), rs1045411(+1177G/A) and rs2249825(+3814C/G) loci in tuberculosis group and control group was performed by PCR and Sanger sequencing. Association between HMGB1 gene polymorphism and susceptibility to PTB in two groups was studied with allele frequency, genotype frequency, and four genetic models (co-dominance, dominance, recessiveness and over-dominance). Results Genotype distribution of all loci conformed to Hardy-Weinberg equilibrium. There was significant difference in allele frequency at +1177G/A locus between two groups (OR, 1.485[95%CI, 1.110-1.986], P=0.007), there was significant difference in genotype distribution between two groups (P<0.05); in the co-dominance model of 1177G/A locus, AG genotype (OR,1.447[95% CI, 1.025-2.041], P=0.035) and AA genotype (OR, 2.812[95%CI, 0.985-8.033], P=0.045) were associated with susceptibility to PTB compared with GG genotype; the dominant model of +1177G/A locus ([AG+AA] vs GG, OR, 1.524[95% CI, 1.090-2.131], P=0.014) was also associated with the susceptibility to PTB; there was no significant difference between the recessive model and the over-dominant model of +1177G/A locus (P>0.05). There was no significant difference in allele and genotype distribution between -1615A/G and +3814C/G loci (P>0.05). Conclusion The polymorphism of rs1045411 (+1177G/A) of HMGB1 gene may be associated with the susceptibility to PTB, allele A of HMGB1 gene may be a susceptible gene of PTB, and carrying of rs1045411(+1177G/A) allele A may increase the risk of developing PTB.