Abstract: Efferocytosis is a physiological process by which phagocytes remove apoptotic cells. Effective efferocytosis is essential for the maintenance of tissue homeostasis. However, defective efferocytosis may cause insufficient clearance of apoptotic cells, then trigger secondary cell necrosis and release of pro-inflammatory factors, resulting in tissue inflammatory response and autoimmune reaction. Accordingly, defective efferocytosis underlies many chronic inflammatory diseases and autoimmune diseases. This review summarizes the recent research progress concerning the molecular mechanisms of efferocytosis and defective efferocytosis in inflammation-related diseases, such as atherosclerosis and systemic lupus erythematosus, in order to provide new therapeutic strategies and theoretical evidence for the prevention and treatment of inflammation-related diseases.