Hepatic LRP1 correlates with malignant progression and poor prognosis in HCC patients, and LRP1 knockdown promotes HCC cell tumorigenicity by enhancing NF‐κB O‐GlcNAcylation and thereby activating Bcl‐2 transcription, which can be reversed by overexpression of the LRP1 β‐chain, thus implicating a potential therapeutic strategy for HCC. This evidence concerns the gene NFKB1 and hepatocellular carcinoma.