Herein, we identified that down-regulation of ABCC4 expression enhanced intracellular cAMP accumulation and noticeable deficiency of G1-S phase checkpoint in cell cycle following irradiation, which might help in explaining the mechanism by which radiation induced apoptosis of CRC cells with decreased ABCC4 expression by shRNA knockdown. The gene discussed is ABCC4; the disease is colorectal carcinoma.