Lung cancer is one of the leading causes of cancer-related death worldwide. Curcumin has been reported to have an antitumor effect by inducing apoptosis and suppressing growth of tumor cells. However, the mechanism by which curcumin exerts its anti-cancer effect needs further research. The purpose of the present study was to identify a miRNA-mediated mechanism which plays a role in the anti-cancer effects of curcumin. Alterations in miRNA expression were seen in curcumin-treated A549 cells, including significant downregulation of miRNA-186* expression by microarray analysis and real-time PCR. The miRNA-186* functions by overexpression or inhibition were investigated using biological assays in A549 cells. Additionally, caspase-10 was identified as a target of miRNA-186* using dual luciferase reporter assays and western blot analysis. These results demonstrate that curcumin induces A549 cell apoptosis through a miRNA pathway. Also, miRNA-186* could serve as a potential gene therapy target in curcumin treatment. furthermore, caspase-10 was shown to be a target of miR-186* regulation.