Phosphatidylinositol-4, 5-bisphosphate (PIP2) is an important phosphatidylinositol on the cell membrane. By acting as a second messenger precursor and self-signaling molecule, it controls the targeted localization and activity of its effectors to regulate cells migration, vesicle transport, cell morphogenesis, signal transduction and other processes. Abnormal cell migration leads to a variety of human diseases in humans, including neurodevelopmental abnormalities, Alzheimer"s disease, cancer and cilia disease. As the regulator of cytoskeleton, the pivotal role of PIP2 in cell migration has been widely confirmed. This review will discuss the specific mechanism of the role of PIP2 in cell migration from the point of PIP2 mediated by PIP5KIs associated with talin, Rho family small GTPases and other effectors to regulate adhesion and actin polymerization.