This study attempted to establish single nucleotide polymorphism frequencies of TNF, IL6, IFNG, IL10 and TGFB1 genes among healthy individuals from South and Southeast Brazil. The sample included 108 healthy individuals from South and 106 from Southeast Brazil. Polymerase chain reaction using sequence-specific primers genotyping was performed for these gene cytokines with Cytokine Genotyping Primers (One Lambda, Canoga Park, CA, USA). Differences in genotypic and allelic frequencies between the populations were assessed by chi-square with either Yates' correction or Fisher's exact test. Our investigations showed that there were not any significant differences between these two Brazilian populations for these polymorphisms. A statistically significant difference in the distribution of alleles and genotypes for both IL6 and IL10 genes was observed between the Brazilian population and the African-derived populations. IL6-174GG genotype and allele G and IL10-819CT/-592CA genotypes are more frequent in African-derived populations than in this mixed Brazilian population, while IL10-1082GG genotype is more frequent in our population. This mixed Brazilian population is closer to those of Joinville's, Santa Catarina, and Rio de Janeiro's, Rio de Janeiro (RJ), Euro-Brazilian populations than to those of Salvador's, Bahia, and Rio de Janeiro's, RJ, African-Brazilian populations. These findings have an enormous importance for experimental design and empowering future linkage and association mapping studies of the role of cytokines in human diseases and allotransplantation outcome in Brazil.