Nasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin-10 (IL-10) is known to reduce the production of interferon-gamma (IFN-gamma), we supposed that genetic differences in IL-10 and IFN-gamma expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL-10 and IFN-gamma with NPC. Different IL-10 -1082 G/A and IFN-gamma+874 Tau/Alpha genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL-10 and IFN-gamma polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL-10 and IFN-gamma do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.