The interleukin 12 (IL-12) cytokine, encoded by polymorphic genes, plays a central role in the T helper 1 cell-mediated immunity against tumors. We investigated whether the 3′ untranslated region +1188 A/C polymorphism (rs 3212227) influences the nasopharyngeal carcinoma (NPC) risk in Tunisian patients. DNA analysis of 247 patients and 284 healthy individuals showed a higher frequency of the 1188 C allele and the CC genotype in patients than in controls (P = 0.00001and P = 0.00005) suggesting that the C variant allele is associated with the susceptibility to NPC. Additional testing showed that the homozygous CC genotype is also associated with advanced stage of the tumor extension at presentation (P = 0.022). Our data suggest that the impaired production of IL-12 behaves as a risk factor for NPC occurrence and progression.