Here, we introduce the structure and function of “USP14, USP1, USP10, USP39, USP22, USP9X, USP2, USP7, USP4, USP5, USP29, USP15, USP12, USP16, USP27, USP46, and USP8” in the USP family research progress in HCC. Here, USP27X is linked to hepatocellular carcinoma.