In head and neck cancer-only cohort, TC genotype of EPHX1 rs1051740 was significantly associated with an increased risk of AKD in co-dominant [OR 13.333, 95% CI 1.684–105.533, P = 0.014] and over-dominant models [OR 4.029, 95% CI 1.552–10.455, P = 0.004]. Here, EPHX1 is linked to head and neck cancer.