Glycoproteins of necrotic debris subjected to O-glycosylation, a well-described post-translational modification, acting as DAMPs activate the TLR4/TRIF/NF-κB signaling in tumor-associated macrophages (TAMs) and in conjunction with the increased expression of HIF-1α both in TAMs and HCC cells, accelerate the secretion of IL-1b. This evidence concerns the gene NFKB1 and hepatocellular carcinoma.