With respect to the subgroups categorized by the region, significant association between DAPK promoter methylation and HNSCC was found among the Asian region and the Non-Asia region in the random-effect model (Asian region, OR = 4.43, 95% CI = 2.29–8.58; Non-Asia region, OR = 3.39, 95% CI = 1.18–9.78).The heterogeneity did not decrease remarkably among the region-based subgroup. This evidence concerns the gene DAPK1 and head and neck squamous cell carcinoma.