Using the MHCC-LM3 orthotopic liver tumor model, we consolidated the MOA for PRL3-zumab by providing key evidence demonstrating how intracellular PRL3 oncoprotein can be externalized as surface PRL3 for PRL3-zumab to trigger the host immune system’s canonical pathways of antibody-mediated tumor clearance within tumor microenvironment. Here, PTP4A3 is linked to neoplasm.