The major aim of this study was to investigate the association of the cytokine gene polymorphisms with the development of renal cell carcinoma (RCC). The study included 29 patients with RCC and 50 healthy controls. All genotyping (TNF-alpha, TGF-beta, IL-10, IL-6, IFN-gamma) experiments were performed using sequence-specific primers PCR (PCR-SSP). It was found that TNF-alpha -308 G/G and TGF-beta codon 10-25 T/T-G/C genotypes were significantly higher in frequency in the patients with RCC group compared with the healthy control group. Additionally, the frequency of TNF-alpha -308 G allele was significantly higher in the patients when compared to controls. On the other hand, the frequencies of TNF-alpha -308 G/A, IL-6 C/C and TGF-beta1 codon 10-25 C/C-G/G genotypes were significantly lower in the cancer group compared with the healthy control group. However, after correction for multiple comparisons (Bonferroni), these results did not remain significant. Nevertheless, these findings suggest that the TNF-alpha -308 G/G and TGF-beta codon 10-25 T/T-G/C genotypes may be potential risk factors for RCC, whereas TNF-alpha -308 G/A, IL-6 C/C and TGF-beta1 codon 10-25 C/C-G/G genotypes may be possible protective factors. The number of the cases has to be increased to investigate the independency of these polymorphisms involved in the oncogenesis of RCC.