Background: Allelic single nucleotide polymorphisms (SNPs) in cytokine-encoding genes can affect the degree of cytokine production, and may be related to the tendency to infectious illnesses as well as various clinical consequences. Objectives: The aim of this work was to evaluate the possible role of SNPs in the regions of the IL-10 (-592), , , IL-12 (+1188), IFN-γ (+874), TNF-α (-308), and TNF-β (+252) genes in susceptibility or resistance to brucellosis and its crucial complications. Methods: In a period of one year, 125 patients with acute brucellosis referring to 3 large public teaching hospitals were enrolled in this study. We studied the SNPs of IL-10, IL-15, IL-18, IL-12, IFN-γ, and TNF-α/β genes using the allele specific polymerase chain reaction (AS-PCR) with sequence-specific primers. Results: Frequency of GG genotype in the TNF-α and TNF-β-encoding genes increased significantly by 52% and 31.2% in patient and control groups, respectively. For IFN-γ, TA genotype was found highly enhanced in patients (60%), while the frequency of AA and TT genotypes were higher in controls (23.2% and 26.4%, respectively). The AA and CC SNPs in IL-12 were dominant in both patient (78.4%) and control (14.4%) groups. In the patient group, the GG and TT genotypes had a higher frequency for genes encoding IL-15 (33.6%) and IL-18 (89.6%). Conclusions: Based on the present study, some SNPs within the several cytokine genes, including TNF-α/β (-308/+252), IFN-γ (+874), IL-15 (-367), , and IL-12 (+1188) are related to the susceptibility or resistance to brucellosis. In order to approve the biological consequence of our results, additional investigations should be carried out in larger population groups.