A1874 is really a novel BRD4-degrading proteolysis targeting chimera (PROTAC). In primary cancer of the colon cells and established HCT116 cells, A1874 potently inhibited cell viability, proliferation, cell cycle progression, in addition to cell migration and invasion. The BRD4-degrading PROTAC could induce caspase and apoptosis activation in cancer of the colon cells. In addition, A1874-caused degradation of BRD4 protein and downregulated BRD-dependent genes (c-Myc, Bcl-2, and cyclin D1) in cancer of the colon cells. Considerably, A1874-caused anti-cancer of the colon cell activity was stronger compared to known BRD4 inhibitors (JQ1, CPI203, and that i-BET151). In BRD4-knockout cancer of the colon cells A1874 continued to be cytotoxic, indicating the presence of BRD4-independent mechanisms. Additionally to BRD4 degradation, A1874 cytotoxicity in cancer of the colon cells seemed to be connected with p53 protein stabilization and reactive oxygen species production. Importantly, the antioxidant N-acetyl-cysteine and also the p53 inhibitor pifithrin-α attenuated A1874-caused cell dying and apoptosis in cancer of the colon cells. In vivo, A1874 dental administration potently inhibited cancer of the colon xenograft development in severe combined immuno-deficient rodents. BRD4 degradation and p53 protein elevation, in addition to apoptosis induction and oxidative stress were detected in A1874-treated cancer of the colon tissues. Together, A1874 inhibits cancer of the colon cell growth through both BRD4-dependent and -independent mechanisms.