The heavy metal distributions in size-fractionated atmospheric particulate matters and the associated health risks were investigated in a typical mining and smelting area in Southwest China. The Cd, Cr, Cu, Pb, and Zn concentrations were 19.28, 44.48, 100.0, 554.0, and 601.8 ng/m³, respectively, in PM_2.1; and 23.45, 60.99, 95.25, 559.3, and 813.7 ng/m³, respectively, in PM₁₀. Enrichment factors of heavy metals indicated that anthropogenic sources of Cd, Cu, Pb, and Zn in the size-fractionated particles. The elevated concentrations of Cd, Cu, Pb, and Zn were dominantly enriched in submicron particles (D_P < 1.1 μm), whereas Cr tended to be accumulated in coarse particles (2.1 < D_P < 10 μm). The deposition concentrations for multiple heavy metals in the head airway region, tracheobronchial region, and alveolar regions were 321.07, 21.58, and 51.96 ng/h for children, and 634.49, 42.65, and 102.68 ng/h for adults, respectively. The coarse particles contributed the most to the deposition concentration of HMs in head region, whereas submicron particles had relative higher proportions in the alveolar region. Heavy metals, especially Pb, caused noncarcinogenic risk to the children as the hazard index was 4.45. Moreover, total carcinogenic risks of heavy metals (Cr, Cd, and Pb) were 4.33 × 10⁻⁵ and 7.58 × 10⁻⁵ for adults and children, respectively, indicating potential carcinogenic risks. Overall, the results of this study revealed high health risks to the residents living around the mining and smelting areas, especially the children. It was therefore urgent to control the emission of heavy metals in the atmosphere.