SOCS1 is a critical checkpoint in immune homeostasis, inflammation, and tumor immunity. It plays a central role in regulating cytokine signaling through its ability to inhibit the JAK-STAT pathway. SOCS1 is induced by various cytokines and acts in a negative feedback loop to limit excessive cytokine responses, which can lead to inflammation and autoimmune diseases. In humans, SOCS1 deficiency results in perinatal lethality due to hyperresponsiveness to inflammatory cytokines. SOCS1 also regulates immune cell development and function, particularly in CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages. In cancer, SOCS1 levels are often reduced, leading to enhanced cytokine signaling and resistance to immune checkpoint blockade (ICB) therapies. Targeting SOCS1 has emerged as a potential therapeutic strategy in both autoimmunity and cancer, with approaches including enhancing SOCS1 levels, developing SOCS1-targeting drugs, and combining SOCS1 reduction with ICB. The complex roles of SOCS1 in immune regulation highlight its importance as a therapeutic target in various diseases.SOCS1 is a critical checkpoint in immune homeostasis, inflammation, and tumor immunity. It plays a central role in regulating cytokine signaling through its ability to inhibit the JAK-STAT pathway. SOCS1 is induced by various cytokines and acts in a negative feedback loop to limit excessive cytokine responses, which can lead to inflammation and autoimmune diseases. In humans, SOCS1 deficiency results in perinatal lethality due to hyperresponsiveness to inflammatory cytokines. SOCS1 also regulates immune cell development and function, particularly in CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages. In cancer, SOCS1 levels are often reduced, leading to enhanced cytokine signaling and resistance to immune checkpoint blockade (ICB) therapies. Targeting SOCS1 has emerged as a potential therapeutic strategy in both autoimmunity and cancer, with approaches including enhancing SOCS1 levels, developing SOCS1-targeting drugs, and combining SOCS1 reduction with ICB. The complex roles of SOCS1 in immune regulation highlight its importance as a therapeutic target in various diseases.