Abstract: In the medical context of precision medicine, the treatment of non-small cell lung cancer(NSCLC) is gradually individualized with the advent of a large number of molecular targeted drugs. The discovery of EML4-ALK fusion gene and Crizotinib which is an oral multi-target (ALK/c-MET/ROS1) tyrosine kinase inhibitor has opened another door for targeted therapy on advanced NSCLC. A number of studies have demonstrated that Crizotinib as the first-line, second-line or multi-line treatment for the gene-related NSCLC including ALK or ROS1 positive NSCLC is safe and effective. However, acquired resistance to Crizotinib will develop after treatment for 10-12 months; the mechanisms of resistance are complex and diverse, so, overcoming the problem of resistance is a huge challenge now. In this paper, we summarize the therapeutic targets, efficacy, mechanisms of resistance and treatments after resistance to crizotinib in NSCLC; the aim is to provide some clinical guidance for the choice of molecular-targeted drug and treatments after drug resistance.