Abstract: Lorlatinib (PF-06463922) is a highly selective and potent third generation anaplastic lymphoma kinase (ALK) inhibitor with dual activity against c-ros oncogene 1, a receptor tyrosine kinase (ROS1). In November 2018, the US Food and Drug Administration approved lorlatinib for treatment of disease progression in ALK-positive and late-stage NSCLC patients who receive the treatment with crizotinib and at least one of other ALK inhibitors; and those with disease progression after treatment of alectinib or ceritinib as the first ALK inhibitor. The results of phase I/Ⅱ clinical trials showed that it has effective initial anti-tumor activity, strong intracranial therapeutic activity, with less tolerance and safety issues. This paper systematically reviewed the chemical structure, mechanism of action, pharmacodynamics, pharmacokinetics, usage and dosage, clinical research, safety and upcoming research fields of lolatinib, to provide an update on clinical or laboratory research and clinical practice.