Our results showed that the expression level of NOS2 could induce the opposite expression of GPX4, which might demonstrate that NOS2 can participate in GPX4 synthesis or breakdown, repress NF-κB pathway by inhibiting the phosphorylation of the p50 and p65, and thus regulated the ferroptosis in CRC cells. This evidence concerns the gene NFKB1 and colorectal carcinoma.