In this study, we firstly discovered that OICR-9429 inhibited the stem-like traits of CRC cells by blocking ABCG2 activation induced by TOX3\WDR5\H3K4me3 complex, being manifested by the suppressed proliferative potential, the down-regulated stem-like traits-related protein markers and the attenuated spheroid-forming ability in cCSCs upon OICR-9429 treatment. The gene discussed is WDR5; the disease is colorectal carcinoma.