In the present study, we show that the HOPX-β promoter is hypermethylated in approximately 50% of OSCC and NPC cell lines and that treatment of an OSCC cell line with a demethylating drug restored HOPX expression, suggesting that promoter methylation is in part responsible for the loss of HOPX expression in HNSCCs. This evidence concerns the gene HOPX and nasopharyngeal carcinoma.