Instead, we found obvious activation of the NF‐κB/Bcl‐2 anti‐apoptotic signaling pathway in parallel with enhanced tumorigenicity in LRP1‐knockdown HCC cells, which was attributed to increased O‐GlcNAcylation of NF‐κB p65 and the consequent upregulation of its anti‐apoptotic activity. Here, LRP1 is linked to hepatocellular carcinoma.