Our main findings are as follows: (1) crizotinib blocks TGFβ-induced Smad activation in NSCLC cells via an ALK/MET/RON/ROS1-independent mechanism; (2) crizotinib directly inhibits TβRI kinase activity in a competitive inhibitory manner; (3) crizotinib suppresses TGFβ- and HGF-induced cell migration and invasion in NSCLC cells; and (4) crizotinib exerts antimetastatic activity in NSCLC cells in vivo without affecting cell growth. The gene discussed is ALK; the disease is non-small cell lung carcinoma.