This study aims to identify the effect of oridonin on proliferation,apoptosis and autophagy of non-small cell lung cancer (A549,H1299) cells,and to clarify its potential mechanism of action.Different concentrations of oridonin were used to intervene in A549 and H1299 cells,and the cell viability assay cell counting kit-8 (CCK8) was used to detect the cell activity and screen the optimal concentration of the drug;10 and 50 μg/mL oridonin and 5 μg/mL cisplatin were used to intervene in A549 and H1299 cells for 24 h,and the effects of oridonin on the proliferation,apoptosis and autophagy of A549 and H1299 cells were observed by flow cytometric counting.Flow cytometric counting was performed to observe the effect of oridonin on apoptosis of A549 and H1299 cells.Detecting the expression of cysteine aspartate protease 3 (Caspase3),cleaved-cysteine aspartate protease 3 (Cleaved-Caspase3),B-cell lymphoma-2,Bcl-2,cysteine aspartate protease 9 (Caspase9),microtubule-associated protein light chain 3 isoform I\\II(LC3I\\II),Bax,p62,Beclin-1 protein;A549 cells overexpression of Beclin-1 and addition of 50 μg/mL oridonin,WB detection of Beclin-1-related proteins.oridonin concentration-dependently inhibited the proliferation of A549 and H1299 cells (P＜0.05),with IC₅₀ values of 38.2 and 46.6 μg/mL,respectively;oridonin enhanced the expression of Bax,Cleaved-Caspase3,Caspase3,Caspase9,and p62 in A549 and H1299 cells (P＜0.05) and inhibited LC3-I,LC3-II,and Beclin-1 protein expression in A549 and H1299 cells (P＜0.05);and oridonin reduced Beclin-1,LC3-II,and p62 protein expression in overexpressing Beclin-1 non-small cell lung cancer cells (P＜0.05).The mechanism by which oridonin could inhibit the activity of NSCLC cells in vitro may be related to the inhibition of Beclin-1 protein expression to reduce autophagy and induce apoptosis.