Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis. Variants in the leptin receptor gene have potential associations with renal cell carcinoma (RCC). We aimed to investigate association of rs1137101 (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123 individuals were classified into group I: 73 RCC patients and group II: 50 healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR technique. GG genotype was the most frequent among RCC patients (67.1%), while AA genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype, and grade were found to affect survival significantly; however, the multivariate analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage significantly affect survival. LEPR gene variants rs1137101 might be a candidate risk factor for RCC in Egypt. GG genotype is associated with more aggressive tumor behavior and shorter survival compared with GA & AA genotypes so, genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.