Recent studies have focused on genetic polymorphism of the interleukin-6 (IL-6) gene, which has led to a better understanding of the intricate interactions between host response, microorganisms, and genetics. Genotype prevalence appears to vary by the race and ethnicity of the population studied. We used a polymerase chain reaction technique to determine the prevalence of single nucleotide polymorphism in IL-6 at position -174 G>C in a population of 30 South Indians. Blood samples were collected from 15 chronic periodontitis patients and 15 healthy controls. The results showed that the G/G genotype was significantly more frequent in the chronic periodontitis group and that the C/C genotype was significantly more frequent in the control group (P = 0.0069 for both). The G allele was more frequent in chronic periodontitis patients (76.67%), whereas the C allele was more frequent in the control group (73.33%). Among chronic periodontitis patients, the odds ratio for having the G allele, as compared with the controls, was 9.04. In this population, the presence of the G/G genotype of IL-6 (-174) might increase susceptibility to chronic periodontitis, whereas the C/C genotype may have a protective effect.