ADAM9 protease plays a key role in the shedding of MHC class I related chain A (MICA) that regulates the sensitivity of tumor cells to natural killer cells (NK). The expression of ADAM9 in CD133si-PLC/PRF/5 cells and CD133-Huh7 cells decreased, membrane-bound MICA increased, and soluble MICA production decreased. CD133si-PLC/PRF/5 cells and CD133-Huh7 cells are both sensitive to NK activity, which depends on the expression level of membrane-bound MICA, while HCC cells expressing CD133 are not. Here, MICA is linked to hepatocellular carcinoma.