This study demonstrates for the first time that, in CRC cells, the transcription coregulator RIP140 (1) strongly cross‐talks and directly interacts with the HES1 transcription factor, (2) is engaged in the autoregulation of its oscillatory expression, (3) reverses its mitogenic activity on cancer cell proliferation, and (4) is required to reveal its correlation with prolonged patient survival. This evidence concerns the gene HES1 and cancer.