PDZ-binding kinase (PBK), a member of the mitogen-activated protein kinase kinase (MAPKK) family, is a silk-threonine kinase containing 322 amino acids. Its protein is mainly expressed in the tissues with high proliferation potential, testis, placenta, activated T cells and neural progenitor cells while extremely low in the tissues and cells with a high degree of differentiation. In recent years, PBK expression has been found significantly enhanced in a variety of malignant tumor such as breast, colon, liver, lung, prostate, esophageal cancer, and so on, closely related to poor prognosis of the cancers mentioned above. Further studies have pointed out that PBK can also promote the proliferation, invasion and metastasis of many cancer cells through a series of complex signaling pathways including Wnt, PI3K/AKT/mTOR, MAPK, FOXM1, nuclear factor-κB and matrix metalloproteinase (MMP), and participate in drug resistance. Moreover, the role of PBK has been confirmed controlled by different microRNA like miR-216b-3p, miR-770-5p and miR-372-5p in the cancers. All above suggest that PBK might be a new proto-oncogene, which is expected to become a new molecular target for tumor suppressor drugs.