Taken together, this study demonstrated that Rapa combined with Osi reduced cell viability, proliferation, and migration, regulated the cell cycle, and increased the ROS level, apoptosis, and autophagy of A549 and PC-9 cells by activating the PARP pathway and inhibiting the MAPK/EKR and Akt/mTOR pathways, providing a novel theoretical basis for their clinical treatment of NSCLC. This evidence concerns the gene MTOR and non-small cell lung carcinoma.