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.