Hence, our combined unbiased proteomic, functional and bioinformatic analysis suggests that LUBAC- and linear ubiquitin-dependent LTβR-derived canonical NF-κB signaling is responsible for triggering the secretion of the pro-inflammatory chemokines IL-8 and CCL20 which, in turn, could potentially drive tumor progression and negatively impacts HCC patient survival. This evidence concerns the gene CXCL8 and hepatocellular carcinoma.