Background: Colonic lining epithelium is subject to variety of insults ranging from inflammatory, infectious to neoplastic processes. One of the most common colon problems are inflammatory bowel disease, colorectal polyps, cancerous growths. Caspases are involved in apoptosis, necrosis, and inflammation. Altered Caspase activity has been associated with a variety of colonic diseases, including inflammatory bowel disease (IBD) and colorectal cancer. Caspases-4 and -5 involvement during intestinal homeostasis and disease has not yet been established. Aim: Detection of the tissue expression of Caspases-4 and -5 in some chronic colorectal diseases. Methods: 100 patients underwent colonoscopy divided into four groups: colorectal cancer (CRC) (35 patients), inflammatory bowel disease (IBD) (25 patients), colorectal polyp (CRP) (20 patients) and irritable bowel syndrome (IBS) as control (20 patients). The diagnosis was established on the basis of clinical history, laboratory (CBC, ESR, liver function tests, CEA), endoscopic and histological data. Immunohistochemistry (IHC) techniques were employed to examine the cellular expression profile of Caspase-4 and -5. Results: Tissue Caspase-4 and -5 were statistically highly significantly increased in the epithelium of CRC in comparison to the other groups. On the other hand, stromal expression of Caspase -4 and -5 were statistically highly significantly increased in IBD group in comparison to the other groups. Conclusions: This study identified epithelialexpressed Caspases -4 and -5 as biomarkers with diagnostic potential in CRC. Also they were a potential marker of dysplasia in IBD and colorectal polyps.