In the present study, we acquired both in vitro and in vivo evidence supporting the critical role of SLC34A2 in the induction of ROS-HIF-1-EZH2 signaling pathway in the proliferation and chemo-resistance of CRC, suggesting that SLC34A2 inhibition supplies a potential therapeutics in CRC. The gene discussed is SETD2; the disease is colorectal carcinoma.