The renal cell carcinoma (RCC) is a rare condition, accounting for only 3% of all adult malignancies althoughconstituting 90% of kidney cancers. The tumor is immunogenic and the host immune system may modulate theclinical course of the disease. It has been reported that genetic polymorphisms in the interleukin-4-receptoralpha gene are associated with risk and prognosis in RCCs. The present study is aimed at analyzing the presenceand significance of the interleukin-4-receptor alpha Ile50Val and Gln576Arg polymorphisms in a group of RCCpatients from South India. PCR-RFLP analysis was performed on genomic DNA isolated from blood samplesand the genotypes deduced. A significant association was found between the IL4 R alpha Val/Val genotype andincreased risk of RCC (OR: 3.45, CI: 1.15–10.38, P: 0.04). The Val/Val genotype was also found to be significantlyassociated with increased risk in individuals below 54 years (OR: 5.79, CI: 1.33–25.07 P: 0.03) of age and infemales (OR: 7.47, CI: 1.4–39.84, P: 0.03). However, no significant association was observed with the Gln576Argpolymorphism. Stratified analysis based on the genotypes and the stage of tumor revealed no significantassociation. Thus, the present study indicates that IL4Ralpha could be a candidate gene for assessing the risk ofRCC.