Nasopharyngeal carcinoma (NPC) has been known to be associated with HLA class I region. The aim of this study was to investigate the association between HLA-E and genetic susceptibility to nasopharyngeal carcinogenesis by comparing the frequencies of HLA-E alleles in 100 Thai NPC patients and 100 healthy controls. HLA-E typing was performed by means of polymerase chain reaction-sequence-specific oligonucleotide probe method. The frequency of the HLA-E*0103 allele and HLA-E*0103, 0103 genotype, but not others, was increased in NPC patients, compared to controls. This observation suggests a possible role for HLA-E in NPC development, possibly via natural killer cell or cytotoxic lymphocyte function.