MiR-335 was downregulated in multi-drug resistant cell lines of human SCLC. Overexpression of miR-335 sensitized human SCLC cells to chemotherapy and radiotherapy. Overexpression of miR-335 promoted cell apoptosis and inhibited cell migration ability of human SCLC in vitro. Overexpression of miR-335 inhibited tumor growth in vivo. PARP-1 was a direct target gene of miR-335, and NF-κB pathway was involved in the regulation network.