Collectively, in this study we revealed iron exposure could activate ROS and NRF2, resulting in an increasement of Warburg enzymes (LDHA, PGK1, and HK2) and GSH-related proteins SLC7A11 and GPX4, thus enhancing the Warburg effect, counteracting the iron-induced lipid peroxidation and protecting CRC cells from ferroptosis (Figure 8). Here, PGK1 is linked to colorectal carcinoma.