Abstract : Multi-drug resistant tuberculosis (MDR-TB) represents a major public health problem on a global scale so the aim of this study was to determine the association of Interleukin-10 (IL-10) rs.1800896 and Interferon-Gamma (IFN-γ) rs.2430561 single nucleotide polymorphisms (SNP) with MDR-TB. 60 tuberculosis patients (30 patients with and 30 patients without MDR-TB) and 30 healthy subjects as controls participated in this study. Serum IL-10 and IFN-γ levels were measured by ELISA. SNPs of IL-10 –rs.1800896 and IFN-γ rs.2430561 genes were detected using allele-specific amplification. IL-10 serum level was significantly higher in TB patients with MDR (57.3±14.8 pg/l) than TB patients without MDR (41.5±8.4 pg/l). Serum IFN-γ was significantly lower among TB patients with MDR (41.7±15.8 pg/l) compared to TB patients without MDR (83.7±25.05 pg/l). The AA genotype of IL-10 rs.1800896 and TT genotype of IFN-γ was significantly higher in the control group than in patient groups. Also The AA genotype of IFN-γ rs.2430561 was significantly higher in patient with MDR than in patient without MDR-TB. Regarding IL-10 GG and AG genotypes was considered risk from MDR TB (OR=11.54 and 4.1 for GG and AG respectively). Regarding INF-γ TT and AT genotypes considered protective for MDR TB (OR=0.09 and 0.17 for TT and AT respectively)