Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway. Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186 * in A549/DDP . In addition, transfection of cells with a miR-186 * inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186 * significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186 * may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.