The present study detected that the expression levels of Meg3 were significantly lower in cisplatin-resistant A549/DDP lung cancer cells, compared with those in parental A549 cells. Furthermore, upregulation of Meg3 was able to re-sensitize the A549/DDP cells to cisplatin in vitro. Whereas downregulation of Meg3, by RNA interference, decreased the sensitivity of A549 cells to cisplatin. The results of the present study also demonstrated that the Meg3-mediated chemosensitivity enhancement was associated with the induction of cell-cycle arrest and increased apoptosis, through regulation of p53, B-catenin and survivin, which is a target gene of the WNT/B-catenin signaling pathway.