Phosphatase of regenerating liver-3 (PRL-3) belongs to a protein tyrosine phosphatase family, and regulates the protein activity by modifying the phosphorylation of tyrosine residues. Previous studies reported that PRL-3 was closely involved in the occurrence, development, metastasis and prognosis of many kinds of malignant tumors. It probably participats in the reconstruction of the cytoskeleton, the regulation of cell adhesion, and the process of epithelial-mesenchymal transition. PRL-3 might be a promising target for developing drugs in cancer treatment. In this paper, we reviewed the research progress in the relationship between PRL-3 and cancer.