Our previous work reported activating transcription factor 1 (ATF1) is a promotive factor of nasopharyngeal carcinoma (NPC) tumorigenesis. This study is to further explore the association between the human ATF1 rs11169571 polymorphism and the risk of NPC occurrence. The association between ATF1 rs11169571 and risk of NPC occurrence was investigated in clinical samples of 560 patients and 661 controls obtained from southern China with high incidence of NPC. The genotypes were detected by PCR‐RFLP. The differential expression activity of alleles ‐T and ‐C was analyzed with CNE‐2 and C666‐1 cells by luciferase reporter assay. Our data suggested that the allelic frequency and genotypes were significantly different between patients and controls. Compared to the TT homozygote, the TC and CC genotypes have been shown to be significantly decreased in NPC patients (OR = 0.494, 95% CI = 0.387‐0.629, P < 0.001 and OR = 0.556, 95% CI = 0.364‐0.851, P = 0.007, respectively). Compared to the ‐T allele, the ‐C allele is a factor of decreased risk in NPC (OR = 0.642, 95% CI = 0.537‐0.767, P < 0.001). Luciferase reporter activity revealed that the ‐T allele confers a higher expression activity than the ‐C allele in CNE2 cells and C666‐1 cells. In conclusion, ATF1 rs11169571 which could affect the expression of ATF1 is associated with NPC risk.