Our in vitro and in vivo data suggest that overexpression of DUB3 and/or KLF4 may activate the DUB3/KLF4 loop to prevent tumor growth and chemoresistance, whereas knockdown of DUB3 and/or KLF4 may block the DUB3/KLF4 loop to facilitate tumor growth and chemoresistance in HCC. The gene discussed is USP17L2; the disease is neoplasm.