Introduction: The present study focuses on the interaction between long non-coding RNA GAS5 and microRNA-205-5p and their roles in cisplatin-induced acute kidney injury. Methods: Human kidney tubular cells (HK-2) were used to simulate acute renal injury induced by cisplatin with the consequent fluctuating expression levels of GAS5 and MIR-205-5p being determined respectively. Furthermore, the modulating effects of miR-205-5p and GAS5 in cisplatin-induced apoptosis of renal tubular epithelial cells and the possible binding sites between them were evaluated. Results: The results depicted that the expression of GAS5 was significantly up-regulated after AKI induced by cisplatin, while inhibiting the increase of expression would alleviate the apoptotic-promoting effect of cisplatin on renal tubular epithelial cells. MIR-205-5p is negatively regulated by GAS5, thus down-regulation of GAS5 will consequently elevate the expression of miR-205-5p and further alleviate the damage of HK-2 cells induced by cisplatin. Conclusions: In conclusion, in cisplatin-induced AKI, the expression of GAS5 was increased and consequently inhibited that of miR-205-5p by direct binding, which eventually aggravate the renal tubular epithelial injury, indicating their potential of being important diagnostic markers and therapeutic targets in the treatment of cisplatin-induced AKI.