To explore the protective effect of the urinary exosomes derived from premature infants on cisplatin-induced AKI and investigate the possible mechanisms by analyzing the miRNAs in the urinary exosomes for the first time, we conducted the in vivo and in vitro studies using cisplatin, and confirmed that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. Here, MAPK8 is linked to acute kidney injury.