Lung cancer represents a significant problem for public health worldwide. Galangin (GG), a natural active compound 3, 5, 7-trihydroxyflavone, is a type of bioflavonoid, which is isolated from the Alpinia galangal root and suggested to induce apoptosis in various cancers. We investigated the ability of Galangin (GG) to attenuate the drug resistance of human lung cancer cells, resistant to treatment of cisplatin (DDP). DDP is a pyrimidine analog, widely used in cancer treatment. Galangin and DDP co-treatment resulted in a dose-dependent suppression of the cell proliferation. Decreasing of p-STAT3 was included in p65 suppression by GG with DDP in combination. Additionally, the presence of GG potentiated the effects of DDP on apoptosis induction through suppressing Bcl-2 in DDP-resistant lung cancer cells. The pro-apoptotic proteins of Bax and Bid were up-regulated, accompanied with Caspases cleavage, leading to apoptosis. Moreover, in mice xenograft models, the combined therapy inhibited tumor growth compared to the GG or DDP treatment alone. Our data indicated a novel therapeutic strategy to potentiate DDP-induced anti-tumor effect in lung cancer cells with DDP resistance by GG through inactivating p-STAT3/p65 and Bcl-2 pathways.