Currently epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is widely used for treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, intracranial metastasis and progression could happen to some patients while their primary tumors in lung stabilize or even shrink after EGFR-TKI treatment. And mechanisms on this phenomenon remain unclear. Recently, increasing studies have demonstrated that it is associated with the pharmacokinetics of EGFR-TKI, heterogeneity between primary tumors and metastases, EGFR mutation status and prolonged survival. Therefore, we write this review to discuss the mechanisms on intracranial metastasis of NSCLC after clinical benefit from EGFR-TKI.