Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have been explored as adjuvant therapies to enhance the efficacy of cytotoxic agents in treating various cancers. These compounds, known for their ability to suppress autophagy, have shown promise in experimental studies and clinical trials. The review discusses the combined application of CQ/HCQ with conventional chemotherapy drugs such as doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinase inhibitors, and PI3K/Akt/mTOR inhibitors. These combinations have been found to increase the sensitivity of cancer cells to cytotoxic agents, reduce tumor growth, and overcome resistance to standard chemotherapy. The mechanisms underlying these effects include the suppression of autophagy, induction of apoptosis, and disruption of intracellular signaling pathways. While most in vitro and in vivo studies have demonstrated the effectiveness of CQ/HCQ in sensitizing cancer cells to chemotherapy, clinical trials have shown inconsistent results. The development of more specific and potent autophagy inhibitors is necessary to improve the efficacy and reduce side effects of CQ/HCQ in cancer treatment.Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have been explored as adjuvant therapies to enhance the efficacy of cytotoxic agents in treating various cancers. These compounds, known for their ability to suppress autophagy, have shown promise in experimental studies and clinical trials. The review discusses the combined application of CQ/HCQ with conventional chemotherapy drugs such as doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinase inhibitors, and PI3K/Akt/mTOR inhibitors. These combinations have been found to increase the sensitivity of cancer cells to cytotoxic agents, reduce tumor growth, and overcome resistance to standard chemotherapy. The mechanisms underlying these effects include the suppression of autophagy, induction of apoptosis, and disruption of intracellular signaling pathways. While most in vitro and in vivo studies have demonstrated the effectiveness of CQ/HCQ in sensitizing cancer cells to chemotherapy, clinical trials have shown inconsistent results. The development of more specific and potent autophagy inhibitors is necessary to improve the efficacy and reduce side effects of CQ/HCQ in cancer treatment.