In this review, we described the sources and characteristics of three different particle sizes of dust: PM2.5, silica, and nanosilica. Based on their respective characteristics, we further explored the main toxicity induced by PM2.5, silica, and nanosilica in vivo and in vitro. Furthermore, we evaluated the health implications of respiratory dust on the human body and proposed potential synergistic effects, taking into consideration current studies. Overall, the severity of organ damage and cytotoxicity induced by PM2.5, silica, and nanosilica varies and is influenced by multiple factors, including dust type, size, dose, and surface composition. Other key factors, such as cell type, cell status, organ distribution, animal status, and the duration of exposure, also play a role and are subject to individual differences in cells and in vivo. The toxicity mechanisms of PM2.5, silica, and nanosilica include oxidative stress, inflammation, DNA damage, and metabolic disorders. Currently, the reported injuries in humans are focused on respiratory diseases, cardiovascular diseases, neurological diseases, and adverse pregnancy outcomes. However, studies on the related signaling pathways are still relatively incomplete.