In conclusion, this study provides fundamental information on the regulatory molecular mechanisms of EGF-induced HO-1 expression through the c-Src, NADPH oxidase, ROS, PI3K, and Akt signaling pathway in increasing NF-κB activation and HO-1 protein expression in human HT-29 colon cancer cells. Here, HMOX1 is linked to malignant colon neoplasm.