To date, radiation therapy (RT)-induced tumor metastasis is widely recognized as a prominent problem which leads to an immense mortality in patients with lung cancer. As the active anti-oxidative components obtained from fruits and beverages such as grapes and red wine, oligomeric proanthocyanidins (OPCs) have been confirmed to exhibit a promising anti-tumor property in previous studies. However, few has put their focus on the impacts of OPCs on tumor post-irradiation progression, particularly on metastasis. This study investigated the advantages of OPCs in RT-elicited lung cancer metastasis. A549-bearing nude mice were administered with OPCs and/or RT treatment. The results indicated that OPCs markedly enhanced the radioresponses such as decreasing tumor’s volume and weight, with a significant reduction of MMP-2/-9 in A549-bearing xenografts (P<0.05). In vitro findings also showed that OPCs presented a striking irradiation synergy. OPCs notably inhibited the migration and invasion in A549 and H446 cell lines (P<0.05) while no obvious inhibition in tumor growth was observed. These effects might be due to the induction of γ-H2AX foci and the remission of EMT elicited by RT (P<0.05), but not the blockage of cell cycle. Our results demonstrated for the first time that OPCs alleviate irradiation-induced tumor prometastatic potential, which highlights a novel profile of OPCs as potent agents for preventing post-radiation recurrence and metastasis in patients with lung cancer.