Taking advantage of a unique series of liver specimens from well-characterized patients with HBV-associated HCC studied at a single center in Italy, we conducted an extensive analysis of the TME in multiple areas of the liver containing HCC by IHC, including CD3, CD8, CD20, alpha-SMA, CD68, CD163, and CD56, and the immune checkpoints CTLA-4 and PD-1 with its ligand PD-L1. This evidence concerns the gene CD274 and hepatocellular carcinoma.