Abstract: Objective To determine the correlation between gene polymorphisms in Wnt signal pathway and susceptibility of Chinese Tibetan people to tuberculosis. Methods A total of 488 active tuberculosis patients and 454 healthy subjects(control) were enrolled in this case-control study. Five single nucleotide polymorphisms (SNPs) in Wnt signal pathway (rs4135385 in CTNNB1 gene,rs11001553 in DKK1 gene,rs56900803 in WIF1 gene,rs7832767 in SFRP1 gene and rs11079571 in AXIN2 gene) were genotyped using MassARRAY method. The genotype and allele distributions of these loci were determined using SPSS19.0 and SNP stats software. Significant SNPs were measured in the co-dominant, dominant and recessive genetic models. The polymorphism distributions of Chinese Tibetans were compared with those of Chinese Han populations. Results The genotype distributions of all SNPs coincided with the Hardy-Weinberg equilibrium in the 2 groups. The frequencies of genotype and allele of rs7832767 in SFRP1 gene were significantly different (P=0.004, 0.002, respectively) between the Tibetan patients with tuberculosis and the Tibetan healthy controls. Compared with C allele carriers, those carrying T allele of rs7832767 showed increased risk of tuberculosis 〔odds ratio (OR)=1.260，95% confidence interval (CI):1.086-1.471，P=0.002〕. The co-dominant, dominant and recessive models of this locus were also associated with higher risk of tuberculosis. No significant differences in genotype and allele distributions were observed for the other four SNP loci (P all>0.05). The distribution of rs4135385 in CTNNB1 gene in the Chinese Tibetan population differed from the Han population (P=0.035 for genotype, 0.021 for allele). There were no obvious differences in genotype and allele distributions for the other four SNPs between the Tibetan and Han populations (P all >0.05).Conclusion SFRP1 gene polymorphism in Wnt signal pathway is associated with tuberculosis susceptibility in Chinese Tibetan population. The distribution of CTNNB1 gene polymorphism differs between Chinese Tibetan and Han populations.