Cisplatin is a widely used and effective chemotherapy drug for various cancers, but it causes nephrotoxicity, a major side effect. Recent research has identified several cellular mechanisms underlying cisplatin-induced kidney injury, including DNA damage, mitochondrial dysfunction, and inflammation. Cisplatin is primarily cleared by the kidneys, where it accumulates and causes damage to renal cells. It can lead to acute kidney injury (AKI), which affects 20–30% of patients. The mechanisms of cisplatin nephrotoxicity involve the accumulation of cisplatin in kidney cells, biotransformation into reactive species, and damage to nuclear and mitochondrial DNA. Cisplatin also triggers apoptosis through various pathways, including the extrinsic and intrinsic apoptotic pathways, and the endoplasmic reticulum stress pathway. Inflammation plays a significant role in cisplatin nephrotoxicity, with cytokines like TNF-α and chemokines contributing to kidney injury. TLR4 receptors are involved in the inflammatory response to cisplatin, and their activation leads to increased production of inflammatory cytokines. Immune cells, including neutrophils, macrophages, T cells, and dendritic cells, are involved in the inflammatory response and contribute to kidney injury. Prevention strategies include hydration, amifostine, and targeting specific pathways such as TLR4 and TNF-α. These strategies aim to reduce cisplatin-induced kidney injury without compromising its anti-tumor effects. Overall, cisplatin nephrotoxicity is a complex process involving multiple pathways, and understanding these mechanisms is crucial for developing effective prevention strategies.Cisplatin is a widely used and effective chemotherapy drug for various cancers, but it causes nephrotoxicity, a major side effect. Recent research has identified several cellular mechanisms underlying cisplatin-induced kidney injury, including DNA damage, mitochondrial dysfunction, and inflammation. Cisplatin is primarily cleared by the kidneys, where it accumulates and causes damage to renal cells. It can lead to acute kidney injury (AKI), which affects 20–30% of patients. The mechanisms of cisplatin nephrotoxicity involve the accumulation of cisplatin in kidney cells, biotransformation into reactive species, and damage to nuclear and mitochondrial DNA. Cisplatin also triggers apoptosis through various pathways, including the extrinsic and intrinsic apoptotic pathways, and the endoplasmic reticulum stress pathway. Inflammation plays a significant role in cisplatin nephrotoxicity, with cytokines like TNF-α and chemokines contributing to kidney injury. TLR4 receptors are involved in the inflammatory response to cisplatin, and their activation leads to increased production of inflammatory cytokines. Immune cells, including neutrophils, macrophages, T cells, and dendritic cells, are involved in the inflammatory response and contribute to kidney injury. Prevention strategies include hydration, amifostine, and targeting specific pathways such as TLR4 and TNF-α. These strategies aim to reduce cisplatin-induced kidney injury without compromising its anti-tumor effects. Overall, cisplatin nephrotoxicity is a complex process involving multiple pathways, and understanding these mechanisms is crucial for developing effective prevention strategies.