Hence, in this study, we investigated the differences in the promoter methylation status of seven immune system genes, EDARADD, GBP4, HAVCR2, HLA DPB1, IL12RB1, MARCO, and SIGLEC12, that could be promising as diagnostic and prognostic biomarkers, and thus in healthy oral mucosa versus oral and oropharyngeal cancers, in order to find out the most eligible biomarkers for those cancers. Here, SIGLEC12 is linked to oropharynx cancer.