There are many environmental, occupational and medical substances that cause dysregulation of autoimmunity. Among these substances, the effects and causative mechanisms of silica particles and asbestos fibers are discussed in this review. Many epidemiological studies have shown a significant association between silica exposure and the occurrence of autoimmune diseases such as rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and anti-neutrophil cytoplasm antibody (ANCA)-related vasculitis. Although the importance of NALP3 inflammasome as the initial immune reaction against silica particles has been recognized, the processes that form the various autoimmune diseases in silica-exposed patients remain unclear. Silica can activate various immune cells and cause an unbalance of regulatory T cells, responder T cells and T helper 17 cells, which might be key factors in understanding the silica-induced autoimmune alteration. In contrast, asbestos exposure shows a smaller association with autoimmune diseases. However, interesting findings have been reported regarding anti-endothelial and mesothelial cell antibodies detected in asbestos-exposed patients. Further investigations may contribute to elucidation of the mechanisms involved in environmental factor-induced modification of autoimmunity. doi:10.11482/KMJ-E42(1)15 (Accepted on May 11, 2016)