To investigate the effect of the combined treatment of Polygonati Rhizoma and Scutellariae Radix on the proliferation and apoptosis of lung cancer cells(H1299 cells)，and the potential biological mechanisms involved.Methods:The cell counting kit-8(CCK-8) assay was used to study the effect of Polygonati Rhizoma and Scutellariae Radix on the inhibition of H1299 lung cancer cell proliferation.Quantitative polymerase chain reaction(qPCR) and Western blot were used to analyze the expression levels of paraoxonase 3(PON3)，phosphoinositide 3-kinase(PI3K)，protein kinase B(AKT)，B-cell lymphoma 2(Bcl2) gene，and Bcl-2-associated X protein(Bax).Additionally，flow cytometry was used to examine the induction of apoptosis by Polygonati Rhizoma and Scutellariae Radix in H1299 cells，as well as changes in mitochondrial membrane potential and reactive oxygen species(ROS) levels.Results:The study found that the combined application of the two drugs significantly inhibited the growth of H1299 cells，with this effect being dose-dependent(P<0.000 1).At the same time，the combination effectively promoted apoptosis of H1299 cells(P<0.05，P<0.000 1)，increased ROS levels(P<0.01)，and damaged the mitochondrial membrane potential(P<0.05，P<0.000 1)，significantly elevated expression levels of Bax，p-PI3K，and p-AKT proteins in H1299 cells，and significantly reduced the expression of PON3 and Bcl2 proteins.Conclusion:The combined use of Polygonati Rhizoma and Scutellariae Radix inhibits lung cancer cell proliferation by downregulating PON3 expression，and induces mitochondrial pathway apoptosis in lung cancer cells through the PI3K/AKT pathway.