Cuproptosis is a newly discovered form of cell death mediated by copper (Cu), distinct from apoptosis, involving the oligomerization of lipoylated proteins and loss of Fe-S clusters. This review summarizes the current understanding of cuproptosis, its mechanisms, and its potential in cancer therapy. Cuproptosis is triggered by Cu ions and involves the accumulation of Cu in mitochondria, leading to the oxidation of lipoylated proteins and the disruption of the TCA cycle, ultimately causing cell death. The mechanism of cuproptosis was first identified in 2019, and further research in 2022 confirmed its role in cancer cell death. Cuproptosis is distinct from other forms of programmed cell death, such as apoptosis, necroptosis, and ferroptosis, and may offer new therapeutic strategies for cancer treatment. Copper plays a critical role in various cancer signaling pathways, including those related to cell proliferation, angiogenesis, and metastasis. Copper ions can activate signaling pathways such as PI3K-AKT, MAPK, and Notch, promoting tumor growth. However, excessive copper can also induce cell death through cuproptosis, which is a promising approach for cancer therapy. Copper ionophores, such as disulfiram (DSF) and elesclomol (ES), are effective in inducing cuproptosis by transporting Cu into cells and mitochondria, leading to the formation of ROS and the disruption of mitochondrial function. Cuproptosis has been shown to enhance antitumor immunity by modulating the cGAS-STING signaling pathway and inducing immunogenic cell death. Additionally, cuproptosis can be used in combination with immune checkpoint inhibitors to improve cancer treatment outcomes. Copper-based nanomaterials have also been explored as potential tools for inducing cuproptosis in cancer cells, with the aim of achieving targeted therapy and minimizing damage to normal cells. Despite the progress in understanding cuproptosis, there are still many unanswered questions, including the exact mechanisms of cuproptosis, the role of biomarkers in predicting cuproptosis, and the optimal Cu concentration for therapeutic effects. Further research is needed to fully understand the potential of cuproptosis in cancer therapy and to develop more effective treatment strategies.Cuproptosis is a newly discovered form of cell death mediated by copper (Cu), distinct from apoptosis, involving the oligomerization of lipoylated proteins and loss of Fe-S clusters. This review summarizes the current understanding of cuproptosis, its mechanisms, and its potential in cancer therapy. Cuproptosis is triggered by Cu ions and involves the accumulation of Cu in mitochondria, leading to the oxidation of lipoylated proteins and the disruption of the TCA cycle, ultimately causing cell death. The mechanism of cuproptosis was first identified in 2019, and further research in 2022 confirmed its role in cancer cell death. Cuproptosis is distinct from other forms of programmed cell death, such as apoptosis, necroptosis, and ferroptosis, and may offer new therapeutic strategies for cancer treatment. Copper plays a critical role in various cancer signaling pathways, including those related to cell proliferation, angiogenesis, and metastasis. Copper ions can activate signaling pathways such as PI3K-AKT, MAPK, and Notch, promoting tumor growth. However, excessive copper can also induce cell death through cuproptosis, which is a promising approach for cancer therapy. Copper ionophores, such as disulfiram (DSF) and elesclomol (ES), are effective in inducing cuproptosis by transporting Cu into cells and mitochondria, leading to the formation of ROS and the disruption of mitochondrial function. Cuproptosis has been shown to enhance antitumor immunity by modulating the cGAS-STING signaling pathway and inducing immunogenic cell death. Additionally, cuproptosis can be used in combination with immune checkpoint inhibitors to improve cancer treatment outcomes. Copper-based nanomaterials have also been explored as potential tools for inducing cuproptosis in cancer cells, with the aim of achieving targeted therapy and minimizing damage to normal cells. Despite the progress in understanding cuproptosis, there are still many unanswered questions, including the exact mechanisms of cuproptosis, the role of biomarkers in predicting cuproptosis, and the optimal Cu concentration for therapeutic effects. Further research is needed to fully understand the potential of cuproptosis in cancer therapy and to develop more effective treatment strategies.