In this case-control comparison study, we found a significant association between CHRNA5 rs3841324 variant genotypes and NPC risk, and individuals with CHRNA5 rs3841324 combined variant genotypes (ins/del+del/del) had an elevated risk compared to the CHRNA5 ins/ins genotype, especially among ever-smokers. This evidence concerns the gene CHRNA5 and nasopharyngeal carcinoma.