Genetic factors are known to be important in the development of nasopharyngeal carcinoma (NPC). Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) at positions -1082 (A/G), -819 (T/C) and -592 (A/C) in the IL-10 gene promoter were involved in predisposing an individual to NPC. One hundred and ninety-eight patients with NPC and 210 age- and sex-matched controls, genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. There were significantly differences in the genotype and allele distribution of -1082 A/G polymorphism of the IL-10 gene among cases and controls. The -1082 AG and GG genotypes were associated with a significantly increased risk of NPC as compared with the -1082 AA genotypes. Haplotype analysis showed that the homozygosity of the GCC haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene conveys the highest risk for NPC compared with the homozygosity for the ATA haplotype. This study shows for the first time an association between IL-10 gene promoter -1082 A/G polymorphism and its haplotype may contribute to genetic susceptibility to NPC in a Chinese population.