Lung cancer is a common type of cancer with a high mortality rate in China. Cisplatin (Cis) is one of the most effective broad‑spectrum chemotherapeutic drugs for the treatment of advanced lung cancer. However, Cis resistance remains an obstacle in the treatment of advanced lung cancer. Pristimerin (Pris), a naturally occurring triterpenoid quinone compound, not only possesses anticancer properties, but also enhances chemosensitivity. Therefore, the present study aimed to investigate whether Pris can enhance the chemosensitivity of lung cancer cells to Cis and identify the underlying mechanism. A Cell Counting kit‑8 and flow cytometry were used to determine cell viability, cell cycle progression and apoptosis in A549 and NCI‑H446 cells. Western blotting was used to determine cell apoptosis‑related, cell cycle‑related and autophagy‑related proteins. The results showed that Pris inhibited cell proliferation, and induced G0/G1 arrest and cell apoptosis in A549 and NCI‑H446 cells. The western blotting revealed that Pris effectively synergized with Cis to induce cell apoptosis by inhibiting the microRNA‑23a/Akt/glycogen synthase kinase 3β signaling pathway and suppressing autophagy. In vivo xenograft experiments confirmed that Pris effectively synergized with Cis to suppress tumor growth. Collectively, these results indicate that Pris synergized with Cis and that this may be a potential therapeutic strategy to overcome lung cancer.