Identifying the nature and extent of atmospheric PM_2.5-bound toxic organic pollutants is beneficial to evaluate human health risks of air pollution. Seasonal observations of PM_2.5-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) in the Yangtze River Delta (YRD) were investigated, along with criteria air pollutants and meteorological parameters. With the elevated PM_2.5 level, the percentage of 4-ring PAHs and typical NPAH including 3-Nitrobiphenyl (3-NBP) and 2-Nitrofluoranthene (2-NFLT) increased by 19–40%. PM_2.5-bound 2-NFLT was positively correlated with O₃ and NO₂, suggesting the contribution of atmospheric oxidation capacity to enhance the secondary formation of NPAHs in the atmosphere. Positive matrix factorization (PMF) analysis indicated that traffic emissions (44.9–48.7%), coal and biomass combustion (27.6–36.0%) and natural gas and volatilization (15.3–27.5%) were major sources of PAHs, and secondary formation (39.8–53.8%) was a predominant contributor to total NPAH concentrations. Backward trajectory analysis showed that air masses from North China transported to the YRD region increased PAH and NPAH concentrations. Compare to clean days, the BaP equivalent concentrations of total PAHs and NPAHs during haze pollution days were enhanced by 10–25 and 2–6 times, respectively. The Incremental Lifetime Cancer Risks (ILCRs) of PAHs by inhalation exposure also indicated high potential health risks in the YRD region. The results implied that the health risks of PM_2.5-bound PAHs and NPAHs could be sharply enhanced with the increase of PM_2.5 concentrations.