Objective:To investigate whether miR-135a/b could modulate the drug resistance of the human lung cancer cell line A549/CDDP to cisplatin(CDDP),and explore the mechanism of miR-135a/b on the CDDP sensitivity of A549/CDDP cells. Methods:MiR-135a/b expression was measured by quantitative real-time PCR. Transient transfection was used in A549 and A549/CDDP cell lines. Cell viability was detected by MTT assay. MCL1 3’-untranslated region-based luciferase reporter plasmids was constructed to testify the target gene of miR-135a/b.Protein expressions were measured by western blot. Flow cytometry was used to detect CDDP-induced apoptosis. Results:We found that miR-135a/b were downregulated while MCL1 was upregulated in A549/CDDP cells,compared with the parental A549 cells. In vitro drug sensitivity assay demonstrated that the over-expression of miR-135a/b sensitized A549/CDDP cells to cisplatin. The luciferase activity of MCL1 3’-untranslated region-based reporter constructed in A549/CDDP cells suggested that MCL1 was the direct target gene of miR-135a/b. Enforced miR-135a/b expression reduced MCL1 protein level and sensitized A549/CDDP cells to CDDP-induced apoptosis. Conclusion:This study demonstrated that hsa-miR-135a/b could play a role in the development of CDDP resistance in lung cancer cell line at least in part by modulation of apoptosis via targeting MCL1.