The cytolytic activity of natural killer (NK) cells on ADAM9KD-HCC cells is higher than that on control cells, and the enhancement of this cytotoxicity depends on the MICA/B and NK group 2, D pathways. Sorafenib treatment resulted in a decrease in the expression of ADAM9 in HCC cells, an increase in the expression of membrane-bound MICA and a decrease in the level of soluble MICA. The addition of sorafenib enhanced the NK sensitivity of HCC cells by increasing the expression of membrane-bound MICA. Here, ADAM9 is linked to hepatocellular carcinoma.