This study examines the potential association between single nucleotide polymorphisms (SNPs) in toll-like receptor (TLRs) genes (TLR-2Arg753Gln (rs5743708, G2258A), TLR-9-1237T/C (rs5743836) and TLR-9 +1174G/A (rs352139)) and tuberculosis (TB) infection. We enrolled 238 Egyptians that included 140 patients newly diagnosed with pulmonary TB and 98 healthy control subjects. All subjects were genotyped for TLR-2 Arg753Gln and TLR-9-1237T/C using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Genotyping of TLR-9 +1174G/A was performed using amplification refractory mutation system-polymerase chain reaction (ARMS–PCR). TLR-2 Arg753Gln and TLR-9 +1174G/A SNPs showed no significant change in genotype/allele distribution, indicating no link between these two SNPs and TB susceptibility. On the other hand, a significant increase in TLR-9 -1237TC genotype (P = 0.012) and C allele (P = 0.009) was found in TB-infected patients compared to normal controls. Haplotype analysis showed a significant decrease in GCG and ATG haplotypes in TB patients (P = 0.004 and P = 0.001, respectively). TLR-2 Arg753Gln and TLR-9 -1237T/C genotype frequencies appeared to be in linkage disequilibrium (LD) (D` = 0.9856, r² = 0.0675). TLR-9 -1237 T/C (5743708) might be associated with increased TB risk in Egyptians. Additional larger-scale epidemiological studies are recommended to validate our results.