Multiple drug resistance is the main reason for chemotherapeutic failure in lung cancer patients with complex molecular mechanisms. LncRNA-MALAT1 plays functional roles in the progression of carcinomas and development of drug resistance. We aimed to identify the role of MALAT1 in DDP-resistant non-small cell lung cancer as well as potential mechanisms. Human lung cancer cell line A549 and the DDP-resistant cell line A549/DDP were used. Cell transfection was performed to establish A549/MALAT1 and A549/DDP/shMALAT1 cells. The qRT-PCR analysis was performed to detect lncRNA-MALAT1 level. Cell viability, colony formation assay, apoptosis analysis, western blot analysis, immunohistochemistry, and animal study were carried out. MALAT1 was upregulated in DDP-resistant A549 cell line. MALAT1 decreased DDP sensitivity in vitro and in vivo by upregulating MRP1 and MDR1 via STAT3 activation. Overexpression of MALAT1 contributed to the DDP resistance and might confer a potently poor prognosis.