In this study, we showed that a blockage of Wnt/PKC signaling could increase the baseline apoptosis and cisplatin-induced apoptosis in NSCLC A549 cells and cisplatin-resistant A549/DDP cells, suggesting that targeting Wnt/PKC noncanonical Wnt signaling may be a potential therapeutic strategy to circumvent chemoresistance in lung cancer treatment. Here, PRRT2 is linked to lung cancer.