Oesophageal cancer is a highly aggressive malignancy, associated with extremely high mortality rates and one of the poorest prognoses in oncology. There are two main types of cancer, classified by histology: oesophagal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). Several biomarkers have been developed to identify patients at high risk of disease progression. Amongst them, p38δ MAPK has emerged as a promising candidate, particularly in ESCC, where epigenetic silencing of the MAPK13 gene through CpG island hypermethylation leads to loss of protein expression. This inactivation has been linked to increased tumour aggressiveness and chemoresistance. The aim of this study was to investigate the role of p38δ MAPK as a potential predictive biomarker of epigenetic therapy response in ESCC.