Although significant progress has been made in the treatment of lung cancer, it remains the leading cause of cancer‑associated mortality. Liriopesides B (LPB) is a natural product isolated from the tuber of Liriope platyphylla, whose effective substances have exhibited antitumor activity in several types of cancer. However, the functions of LPB in non‑small cell lung cancer (NSCLC) require further investigation. Therefore, the present study aimed to investigate whether LPB influences the pathogenic effects of NSCLC. In the present study, it was demonstrated that LPB reduced proliferation, and induced apoptosis and cell cycle arrest in non‑small cell lung cancer cells. CCK‑8 and colony formation assays demonstrated that LPB decreased cell viability and proliferation of H460 and H1975 cells in a dose‑dependent manner. Flow cytometry revealed that LPB significantly induced apoptosis of NSCLC cells, along with changes in the expression of apoptosis‑associated proteins, including an increase in Bax, caspase‑3, and caspase‑8 expression, and a decrease in Bcl‑2 and Bcl‑xl expression. LPB inhibited the progression of the cell cycle from the G1 to the S phase. Furthermore, autophagy was increased in cells treated with LPB. Finally, the expression of programmed death‑ligand 1 was significantly decreased by LPB. In conclusion, the results of the present study highlight a potential novel strategy for the clinical treatment of NSCLC.