Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and chemical carcinogen exposure, genetic susceptibility has been reported to play a key role in the development of this disease. Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with NPC in a Chinese population. We analyzed single-nucleotide polymorphisms of IL-2 gene -330 T/G and +114 T/G in 180 patients with NPC and 200 age- and sex-matched controls, using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods, and serum IL-2 levels were measured by enzyme-linked immunosorbent assay. Serum IL-2 levels were decreased in patients with NPC compared with controls (p < 0.01). There were significant differences in the genotype and allele frequencies of IL-2 gene -330 T/G polymorphism between the group of patients with NPC and the control group (p < 0.05). Moreover, genotypes carrying the IL-2 -330 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in patients with NPC. Carrying the IL-2 -330 G variant allele was associated with a decreased ability to produce IL-2, which may contribute to NPC susceptibility.