Hydrogen sulfide (H₂S) is a gaseous signaling molecule that plays a crucial role in physiological and pathological conditions. Recent studies have shown that H₂S mediates apoptosis in cancer cells through multiple signaling pathways, such as PI3K/Akt/mTOR and MAPK, and may improve cancer treatment by regulating its production and metabolism. H₂S has been shown to promote cancer progression in many tissues but has opposite effects on hepatocellular carcinoma and glioma. The mechanisms by which H₂S induces apoptosis vary depending on its concentration and the type of cancer. H₂S can affect apoptosis through the mitochondrial pathway, the TNF receptor family-mediated pathway, and the ER stress pathway. It has been shown to induce apoptosis in various cancers, including lung, esophageal, gastric, hepatocellular, pancreatic, colorectal, breast, and urogenital cancers. H₂S also plays a role in the regulation of apoptosis in hematologic neoplasms and melanoma. Additionally, H₂S-releasing drugs have been developed to enhance the therapeutic effects of cancer treatments. These drugs can induce apoptosis in cancer cells by modulating signaling pathways and reducing the expression of anti-apoptotic proteins. H₂S is also involved in the regulation of the tumor microenvironment and can act as a shield to protect cancer cells from oxidative stress and hypoxia. However, the detection of H₂S concentration in tissues and cells remains a challenge. Overall, H₂S has a complex role in cancer biology, and further research is needed to fully understand its mechanisms and potential therapeutic applications.Hydrogen sulfide (H₂S) is a gaseous signaling molecule that plays a crucial role in physiological and pathological conditions. Recent studies have shown that H₂S mediates apoptosis in cancer cells through multiple signaling pathways, such as PI3K/Akt/mTOR and MAPK, and may improve cancer treatment by regulating its production and metabolism. H₂S has been shown to promote cancer progression in many tissues but has opposite effects on hepatocellular carcinoma and glioma. The mechanisms by which H₂S induces apoptosis vary depending on its concentration and the type of cancer. H₂S can affect apoptosis through the mitochondrial pathway, the TNF receptor family-mediated pathway, and the ER stress pathway. It has been shown to induce apoptosis in various cancers, including lung, esophageal, gastric, hepatocellular, pancreatic, colorectal, breast, and urogenital cancers. H₂S also plays a role in the regulation of apoptosis in hematologic neoplasms and melanoma. Additionally, H₂S-releasing drugs have been developed to enhance the therapeutic effects of cancer treatments. These drugs can induce apoptosis in cancer cells by modulating signaling pathways and reducing the expression of anti-apoptotic proteins. H₂S is also involved in the regulation of the tumor microenvironment and can act as a shield to protect cancer cells from oxidative stress and hypoxia. However, the detection of H₂S concentration in tissues and cells remains a challenge. Overall, H₂S has a complex role in cancer biology, and further research is needed to fully understand its mechanisms and potential therapeutic applications.