Abstract: OBJECTIVE To investigate the effect of miR-382 on regulating the cytotoxicity of γδT cells to lung cancer cell line A549. METHODS γδT cells amplified in vitro were identified by flow cytometry. LDH release assays were performed to detect the cytotoxicity of γδT cells and miR-382 to A549. RT-qPCR assays were performed to detect the expression of miR-382 in lung cancer tissues and A549 cell line. Bioinformatics and western blot analysis were used to determine whether the expression of c-FLIP was regulated by miR-382. Western blot assays were performed to evaluate the release of Smac/DIABLO and cytochrome c and the activation of caspase-8, caspase-9 and caspase-3. RESULTS miR-382 significantly enhanced the cytotoxicity of γδT cells to A549. Furthermore, miR-382 enhanced the activation of caspase-8, caspase-9, caspase-3 and release of cytochrome C and Smac/DIABLO induced by γδT cells in A549 cells. In addition, transfection with miR-382 downregulated the expression of c-FLIP. Meanwhile, transfection with miR-382 abolished the synergistic effect of miR-382 on γδT cells. CONCLUSION MiR-382 enhances cytotoxicity of γδT cells to lung cancer through downregulating the expression of c-FLIP.