Lung cancer chemoresistance is the most frequent barrier in lung cancer therapy. Recent studies have indicated that microRNAs play a significant role in this mechanism and can function as either tumor suppressor or tumor promoters. However the effect of miRNA in lung cancer chemoresistance is poorly understood. Therefore, in the present study we investigated the role of two distinct miR members, the miR-205 and the tumor suppressor miR-218 in the proliferation, invasion and induction of apoptosis in lung cancer cells after carboplatin treatment. The results showed that miR-205 overexpression in A549 and H1975 lung cancer cells is concurrent with the down regulation of miR-218 and in linked with carboplatin sensitivity and chemoresistance. Interestingly, ectopic miR-218 overexpression reduced cell proliferation, invasion and migration of lung cancer cells, whereas miR-205 rescued the suppressive effect of miR-218 by altering the expression levels of the pro-apoptotic proteins PARP, Caspase 3, Bax and upregulating the anti-apoptotic markers Mcl-1 and Survivin. Taken together our findings imply that the miRNAs miR-205 and miR-218 play a key role in the development of lung cancer acquired chemoresistance and the tumor suppressor role of miR-218 in inhibiting lung cancer cell tumorigenesis and overcoming platinum chemoresistance is significant for future cancer therapeutic approaches.