Crystalline silica (the most abundant form of silicon dioxide) is a natural element that is ubiquitous in the Earth's crust. Chronic personal or professional exposure has been implicated in various pathologies, including silicosis and autoimmune diseases since the early 20th century. More recently, a specific pathogenic role for crystalline silica has been identified through its impact on lung epithelial cells as well as immune cells present at this organism barrier. This review summarizes the current in vitro and in vivo knowledge regarding the physiopathology of crystalline silica at the lung-environment interface, discusses its effects on innate and adaptive immune cells and epithelial cells, and reviews current therapeutic perspectives explored in mouse models to alleviate its impact, especially on autoimmune phenotypes.