NKG2A/CD159a is a transmembrane protein belonging to the CD94/NKG2 family of C-type lectin-like receptors that inhibits innate immune system activation, also known as KLRC1, CD159a, NK cell receptor A and NKG2-A/NKG2-B type II integral membrane protein. NKG2A marks a unique immune effector subset preferentially co-expressing the tissue-resident CD103 molecule, but not immune checkpoint inhibitors. NKG2A blockade therapy operated through CD8 T cells, but not NK cells. The increase in NKG2A expression might be induced by IL-10, which was present at a high level in the plasma of HCC patients. Blocking IL-10 could specifically inhibit NKG2A expression in NK cells. These findings indicate that NKG2A expression is influenced by factors from cancer nests and contributes to NK cell exhaustion, suggesting that NKG2A blockade has the potential to restore immunity against liver tumors by reversing NK cell exhaustion.