Although an activating role for CD96 in human NK cells has been reported [6,11,12], a recent study observed that intratumoral NK cells in hepatocellular carcinoma (HCC) patients with high CD96 expression were functionally exhausted and compromised in the production of anti-tumor cytokines IFN-γ and tumor necrosis factor-α (TNF-α). This evidence concerns the gene CD96 and hepatocellular carcinoma.