Chemotherapy and radiation are often accompanied by complications such as intestinal mucositis. The aim of this study was to assess by immunohistochemical assay the consequences of epirubicin-based therapy applied to onco-hematological patients, on the mucosal cells that undergo apoptosis and on the tight junction proteins, immediately before and after a short time of chemotherapy administration. We assessed the protein expression and distribution of the pro-apoptotic Bax, anti-apoptotic Bcl-2 and effector Caspase-3 as key proteins in apoptosis pathways and the changes in immunopositivity of Claudin-1 and ZO-1 tight junction proteins. Results show that the Bcl-2 family is involved in intestinal damage via Caspase-3 dependent apoptosis of epithelial cells. Additionally, the intestinal mucositis activates other injurious pathways through a dramatic drop in Claudin-1 and ZO-1 expressions, contributing for a while to a structural and functional integrity disruption of the intestinal epithelium.