Our study illustrated the mechanism involved in PGC-1α/TFEB-mediated renal protective effect in cisplatin-induced AKI mice, and the major findings are as follows: i) increasing the expression of PGC-1α via various strategies could alleviate Cisp-induced AKI; ii) PGC-1α ameliorates mitochondrial dysfunction and apoptosis via autophagy-mediated clearance of damaged mitochondria; iii) PGC-1α-activated autophagy was dependent on TFEB. Here, PPARGC1A is linked to acute kidney injury.