Lanzhou, a valley-shaped city in northwestern China, experiences heavy air pollution. This study investigated the relationship between the oxidative capacity and heavy metal composition of the PM10 in Lanzhou. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to examine the heavy metal element composition and an in vitro plasmid assay was employed to study the bioreactivity of airborne PM10. The monitoring data revealed that the mass concentration of Lanzhou PM10 exhibited seasonal variations at both the urban and suburban sites, with higher values in winter and spring, lower values in autumn, and the lowest ones in summer. The results of ICP-MS analysis showed that Zn was the metal present in the highest concentrations in both the whole and water-soluble fractions of PM10 collected at both the urban and suburban sites, followed by Fe, Pb, and Mn. Furthermore, the results indicated that Zn, Cd, and As were present mostly in their soluble forms, while the Fe, Pb, and V were primarily in their insoluble ones. The plasmid DNA assay results indicated that the TD20 values (toxic dosages of PM10 causing 20% of plasmid DNA damage) of the Lanzhou PM10 collected at both the urban and suburban sites ranged from 10 μg/mL to over 1000 μg/mL, and exhibited seasonal variations. The TD20 values were high in spring and autumn, and thus the toxicities were low, while the TD20 values were low in winter and summer, and thus the toxicities were high. For PM10 collected at both the urban and suburban sites, the high concentrations of water-soluble Zn, Fe, Pb, and Mn displayed a strong negative correlation with the TD20 values, suggesting that these metals were likely the major elements responsible for plasmid DNA damage. In addition, meteorological conditions (i.e., lower wind speed and higher relative humidity) during the sampling periods may have caused an indirect increase in oxidative damage to DNA.