In this study, we found that ZIP4 binds to Ephrin-B1 to inhibit the ubiquitination of Ephrin-B1, regulating the Wnt family member 5A (Wnt5A)/Jun N-terminal kinase (JNK)/ZEB1 signaling pathway and promoting EMT, thereby inducing invasion and metastasis of liver cancer cells. This evidence concerns the gene ZEB1 and liver cancer.