Herein, we provide novel insights into the molecular mechanisms underpinning the biology behind chemoresistance in CRC, and demonstrate that EGCG inhibits multiple self-renewal driving pathways including Notch and Bmi1, Ezh2, and Suz12, through upregulation of the expression of key tumor suppressive miRNAs. This evidence concerns the gene EZH2 and colorectal carcinoma.