Respiratory dust of different particle sizes in the environment causes diverse health effects when entering the human body and makes acute or chronic damage through multiple systems and organs. However, the precise toxic effects and potential mechanisms induced by dust of different particle sizes have not been systematically summarized. In this study, we described the sources and characteristics of three different particle sizes of dust: PM2.5 (<2.5 μm), silica (<5 μm), and nanosilica (<100 nm). Based on their respective characteristics, we further explored the main toxicity induced by silica, PM2.5, and nanosilica in vivo and in vitro. Furthermore, we evaluated the health implications of respiratory dust on the human body, and especially proposed potential synergistic effects, considering current studies. In summary, this review summarized the health hazards and toxic mechanisms associated with respiratory dust of different particle sizes. It could provide new insights for investigating the synergistic effects of co-exposure to respiratory dust of different particle sizes in mixed environments.