In general, we speculate that SIRT1/PGC-1α/PPAR-γ signaling may represent a molecular metabolic mechanism underlying hypoxia-induced chemoresistance in the NSCLC microenvironment, and targeting hypoxia-related metabolic adaptation may be a potential therapeutic strategy for overcoming chemoresistance in NSCLC. This evidence concerns the gene PPARGC1A and non-small cell lung carcinoma.