Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk for colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, Selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context.