Colorectal cancer is known as one of the most common cancer and the third leading cause of death worldwide. Nrf2 is considered as a main transcription factor for producing antioxidants in response to oxidative stress and reduce damages to the cell. It also plays a crucial role in drug resistance. In this study, the Nrf2 gene was knocked down in HT-29 cell line and then the protein expression profile were investigated by TMT based LC MS/MS approach.