Background: Mycobacterium tuberculosis is a known to cause chronic tuberculosis with high morbidity and mortality, especially in developing countries. Genetic variability of the host determines the susceptbility to the tuberculosis infection. The present study was to evaluate the association of genetic polymorphism among cytokines, also to evaluate the effect of different gene combinations of IFN gamma and its regulating cytokine genes. Aim: To evaluate the presence of single nucleotide polymorphism associated with the genes IFN (+874 A/T), TNF  (-308 G/A), IL-10 (-1082 G/A) among the tuberculosis patients compared with the healthy human controls, as well as study of IFN  gene combination with IL-10 and TNF  in Hyderabad region of the Southern part of India. Materials and Methods: A case control study was conducted, genomic DNA was extracted from peripheral blood samples from both TB confirmed cases and from healthy controls. The association of single nucleotide polymorphism in IFN (+874 A/T), TNF  (-308 G/A), IL-10 (-1082 G/A) was investigated by polymerase chain reaction amplification refractory mutation system. (ARMS-PCR). IFN  gene (+874 A/T) functional single nucleotide polymorphismcombinations in TNF (-308A/G), IL-10 (-1082 A/G) were analyzed.A total of 155 healthy controls and 150 cases were included in the study. Results: We found TNF (-308A/G), GG genotype (OR- 0.423, 95% CI-0.262-0.682, p=0.001) was significantly associated with the tuberculosis incidence. No signficant correlation between IFN (+874 A/T) A or AA , IL-10 (-1082 A/G) G or GG , allele or genotype respecitvley in tuberculosis patients was seen. A multi gene combination study, we found combination of IFN  TA In IL-10 AA hi (OR-1.63, 95% CI- 0.01-2.64, p=0.043) and IFN TA In- TNF GG low (OR-4.14, 95% CI-2.31-7.42, p=0.00) were associated with the tuberculosis cases. Conclusion: From our study we found that genetic variability TNF (-308A/G), GG genotype and multi gene combination IFN  TA In IL-10 AA hi and IFN TA In- TNF GG low are associated with tuberculosis infection.