Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide, affecting up to a third of the global population. While simple hepatic steatosis is often asymptomatic, approximately 25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis, and hepatocellular carcinoma. Liver inflammation and fibrosis are key determinants of prognosis. The pathophysiology of liver inflammation involves diverse factors and immune responses, particularly innate and adaptive immunity. Innate immune mediators such as proinflammatory cytokines, adipokines, inflammasomes, and various cell types like mononuclear cells, macrophages, and natural killer cells play crucial roles in directing the inflammatory process in MASLD. Excess lipids, lipotoxicity, insulin resistance, and molecular patterns derived from gut commensals drive the activation of innate immunity. Targeting pathways of innate immunity may be a promising therapeutic strategy for managing MASLD and its complications. The article focuses on the role of innate immunity in MASLD, highlighting the importance of proinflammatory cytokines, adipokines, inflammasomes, and various cell types in the development and progression of the disease.Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide, affecting up to a third of the global population. While simple hepatic steatosis is often asymptomatic, approximately 25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis, and hepatocellular carcinoma. Liver inflammation and fibrosis are key determinants of prognosis. The pathophysiology of liver inflammation involves diverse factors and immune responses, particularly innate and adaptive immunity. Innate immune mediators such as proinflammatory cytokines, adipokines, inflammasomes, and various cell types like mononuclear cells, macrophages, and natural killer cells play crucial roles in directing the inflammatory process in MASLD. Excess lipids, lipotoxicity, insulin resistance, and molecular patterns derived from gut commensals drive the activation of innate immunity. Targeting pathways of innate immunity may be a promising therapeutic strategy for managing MASLD and its complications. The article focuses on the role of innate immunity in MASLD, highlighting the importance of proinflammatory cytokines, adipokines, inflammasomes, and various cell types in the development and progression of the disease.