Objective To explore the mechanism of β-elemene reversing drug resistance of lung adenocarcinoma based on Notch signaling pathway.Methods A549/DDP cells were treated with β-elemene in a concentration that was not cytotoxic to A549/DDP cells. Designed β-elemene group and control group. Cells in the two groups were given different concentrations (0.25, 0.5, 1, 2, 4, 8, 16, 32 μg·mL^-1) of DDP for 24 h. Cell viability and the IC₅₀ were measured by MTT, and cell apoptosis were detected by flow cytometry. The apoptosis-related proteins (cleaved-caspase 3, cleaved-caspase 9), drug resistance-associated proteins (P-gp, survivin, p21) and Notch signaling pathway proteins (Notch1, Hes1, Hey2) were detected by Western blotting. After A549/DDP cells were treated with β-elemene +1 μg·mL^-1 Notch signaling pathway activator rhNF-κB, compare the IC₅₀ between the β-elemene group and β-elemene + rhNF-κB group, and detect the proteins P-gp, Notch1, Hes1 and Hey2 with Western blotting.Results When the concentration of β-elemene was lower than 20 μg·mL^-1, the inhibition rate of A549/DDP cells was lower than 10%, showing no cytotoxicity. The IC₅₀ of DDP in A549/DDP cells in β-elemene group was lower than that in control group (t=14.712, P<0.05), and the reversal fold was 4.452 times. The apoptosis rate in the β-elemene group was higher than in the control group, and the expression levels of apoptosis-related proteins (cleaved-caspase 3 and cleaved-caspase 9) were higher than those of the control group (P<0.05). The relative expression levels of P-gp and survivin proteins in β-elemene group were lower than in control group, and the relative expression level of p21 protein was higher in β-elemene group than in control group (P<0.05). The relative expression levels of Notch1, Hes1 and Hey2 proteins in β-elemene group was lower than that in control group (P<0.05). The A549/DDP cells in β-elemene + rhNF-κB group had a higher DDP IC₅₀ than that in the β-elemene group, and the expression levels of P-gp, Notch1, Hes1, Hey2 proteins were higher than those of the β-elemene group (P<0.05).Conclusion β-elemene can promote apoptosis of A549/DDP cells by inhibiting Notch signaling pathway, so that can reverse the drug resistance of lung adenocarcinoma.