In the present study, we have shown that downregulation of TFAM inhibits NSCLC tumorigenesis through reducing cellular bioenergetics, activating the ROS-mediated JNK/p38 MAPK and p53/p-p53(ser15)/p21 signaling pathway in NSCLC cells (Figure 6). The gene discussed is TFAM; the disease is non-small cell lung carcinoma.