NUDT21 inhibited HCC proliferation, metastasis and tumorigenesis, at least in part, by suppressing proteasome subunit beta type-2 (PSMB2) and CXXC-type zinc finger protein 5 (CXXC5), acting as a tumor suppressor in hepatocellular carcinogenesis. Here, NUDT21 is linked to hepatocellular carcinoma.