Pharmacological activation of NF-κB using PMA significantly counteracted emodin’s effects on critical regulators including antioxidant proteins (SLC7A11, GPX4), autophagy markers (LC3B, P62), and iron metabolism proteins (NCOA4, FTH1) in CRC cells and PMA partially reversed cytoplasmic iron accumulation, as well as MDA and lipid peroxidation. Here, SLC7A11 is linked to colorectal carcinoma.