Abstract Tuberculosis remains one of the major health burden worldwide; with substantial mortality in Indian population. Several host gene polymorphisms have been studied wherein association between variations in host genes and susceptibility or resistance to tuberculosis have been reported. In the present study, we aimed at investigating the effect of polymorphisms of CCL2, CCR2 and TLR4 genes on risk of acquiring tuberculosis in Indian population. The CCL2 (−2518A/G) and TLR4 (D299G or 896A/G & T399I or 1196C/T) gene polymorphisms were studied by PCR-RFLP method, while the CCR2 (V64I or 190G/A) gene polymorphism was done by ARMS-PCR method. Our findings revealed that the frequencies of the risk alleles ‘G’ and ‘T’ of TLR4 896 A/G and 1196C/T polymorphisms were significantly (p = 0.05) higher in TB cases than in healthy controls with higher odds (OR = 1.73 and 1.78 respectively). The risk allele ‘A’ of the CCR2 190G/A gene polymorphism showed a trend towards increased frequencies of ‘GA’ and ‘AA’ genotypes in TB patients as compared to healthy subjects with higher odds (2.06) of developing TB when in homozygous (AA) condition. Our findings indicate that the presence of variant alleles of genes CCR2 (190 G to A) and TLR4 (896A/G & 1196C/T) make Indian population vulnerable towards developing tuberculosis. Further, analysis with larger sample sizes is required to support our findings, which may allow application of these biomarkers for better management of tuberculosis in Indian population.