A growing body of evidence suggests that host genetic factors play an important role both in susceptibility to HIV infection and progression to AIDS. The present study aimed at evaluating the role of IL-6 and IL-10 gene polymorphisms on the risk of HIV susceptibility and disease progression among North Indian patients. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were applied to genotype IL-6 and IL-10. 300 seropositive and an equal number of age- and sex-matched seronegative control subjects were recruited for this study. There was statistically no significant variation in the frequencies of IL-6 and IL-10 genotypes among cases and controls. However, statistically non-significant association for risk of rapid disease progression was observed due to the combined effect of the IL-6 homozygous CC genotype and CC of IL-10, OR = 1.62, 95% CI = 0.38-6.91. Therefore, combined effects of the CC of IL-6 and CC of IL-10 might reduce the hosts ability to hinder viral replication after infection.