Nasopharyngeal carcinoma (NPC) is a particular entity of head neck cancer, tightly related to Epstein–Barr virus infection and thus to HLA genes. In this study, we aimed to analyze HLA-E polymorphism in NPC advent and prognosis.130 unrelated patients with CNP and 180 unrelated and healthy controls were included in our study. HLA-E genotyping was performed by PCR/RFLP method; SPSS (13.0) was used for statistical analysis, and survival curbs were established with the “Kaplan–Meier” method (Log Rank<0.05).We found a significant difference within HLA-E*103 variants between patients and controls: E*1031 and E*1032 were associated with CNP (OR=1.613, p=0.013 and OR=1.0809, p=0.055), and E*1033 with controls (OR=0.254, p<10−4).Our study reveals that HLA-E polymorphism is associated with nasopharyngeal cancer. HLA-E expression studies could be used to understand the implication of E*103 variants.