Susceptibility to infectious diseases is influenced by genetic background and efficient cellular immune activation is responsible for protection. In tuberculosis (TB), interferon-gamma (IFNγ) is crucial to control intracellular growth of Mycobacterium tuberculosis while interleukin-10 (IL-10) has an antagonistic role. Tumor necrosis factor (TNF) is a central mediator of granuloma formation and control of bacilli spread synergizing with IFNγ to hamper M. tuberculosis infection. Single nucleotide polymorphisms (SNPs) located at these genes could influence cytokine levels and regulate resistance and susceptibility to TB. The aim of this study was to determine the association of the interferon-gamma gene (IFNG) +874T/A, interleukin-10 gene (IL10) -1082G/A and tumor necrosis factor gene (TNF) -308G/A SNPs with TB in several populations using meta-analysis. We searched for association studies correlating these polymorphisms and TB using pre-established keywords in Medline. Meta-analysis was conducted with random effects models to account for heterogeneity between studies. Eleven studies were included in the IFNG +874T/A meta-analysis, while eight were used for the IL10 -1082G/A, and 10 were employed for TNF -308G/A. Data were analyzed in respect to associations between alleles, genotypes and minor allele carriers. Statistically significant results were found only for IFNG. The +874T allele of IFNG showed a protective significant association (OR = 0.75; 95% CI, 0.634–0.887; P = 0.0008). Though not significant, IL10 presented a trend towards protection when only studies with pulmonary TB patients were considered. This data reinforces the critical importance of IFNG +874T/A as a genetic marker for TB resistance and this information can be used for better design of a TB vaccine.