The combination therapy of metformin and CDDP weakens ERK-mediated phosphorylation of NRF2, enhances its polyubiquitination, and promotes its proteasomal degradation, thereby significantly reducing the levels of NRF2 in A549/DDP and H838 NSCLC cells, promoting ROS-mediated apoptosis. Here, NFE2L2 is linked to non-small cell lung carcinoma.