Early stages of non-small cell lung cancer (NSCLC) can be successfully treated by surgical resection of the tumor, but there is still no effective treatment once it is progressed to metastatic phases. Investigation of NSCLC cancer cell migration, metastasis and development of strategies to block this process is essential to improve the disease prognosis. In the present study, we found that GRB2-associated-binding protein 2 (Gab2) is involved in the migration of NSCLC cells and demonstrated that Gab2 disruption impairs NSCLC cells migration. The requirement of Gab2 in the migration of NSCLC was further confirmed by gene silencing in vitro. In corresponding to this result, over-expression of Gab2 significantly promoted the migratory of NSCLC cells. Finally, we found that Gab2 promotes NSCLC migration through the protein kinase B (Akt) signaling pathway and up-regulation the activity of matrix metallopeptidase (MMP)-2/9. To conclude, our findings suggest a novel mechanism underlying the migration of NSCLC cells which might serve as a new intervention target for the treatment of NSCLC.