Autophagy is a highly conserved catabolic process, whereby unwanted cytoplasmic contents are enclosed by the double-membrane autophagosomes and delivered to the lysosomes for degradation. It is responsible for the recycling of nutrients and cellular components, thus playing a pivotal role in maintaining cellular homeostasis as well as cell survival during stress conditions. Perturbations in autophagy are implicated in multiple diseases, such as cancers and neuro-degeneration diseases. Recent studies demonstrate that autophagy may participate in almost every step of immune responses, including pathogen recognition, antigen processing and presentation, immune cell development and function, and immunoregulation. The pathogenesis of some autoimmune diseases, such as multiple sclerosis and Crohn's disease, has been reported to be associated with dysregulated autophagy. Systemic lupus erythematosus (SLE) is a chronic, potentially fatal autoimmune disease, characterized by dysregulation of immune cells and production of autoantibodies that cause widespread tissue and organ damage. The pathogenesis of SLE remains unclear. With several single nucleotide polymorphisms (SNPs) in autophagy-related gene5 (ATG5) being linked to SLE susceptibility, more and more lines of evidence from animal model, cell biology, immunology, and genetics studies show that autophagy contributes to the occurrence, development, and severity of SLE.