Abstract: The effects of different concentrations of Cu²⁺(10, 50, 100, 500, 1 000, 2 500, 5 000 μg/L) and particle sizes (0.1, 0.2, 0.3, 0.5, 0.7, 1.0, 2.0 μm) of polystyrene microplastics on DNA damage in human acute monocytic leukemia (THP-1 cells) were investigated by singlecell gel electrophoresis experiments. As results, ≥50 μg/L Cu²⁺ caused extremely significant DNA damage to THP-1 cells (p< 0.01). Moreover, the extent of DNA damage in THP-1 cells increased with increasing Cu²⁺ concentration. In the other hand, 2.0-μm particle size polystyrene microplastics (10 mg/mL) produced significant DNA damage in THP-1 cells. Under combined contamination, 25 mg/mL microplastics (2.0 μm) and Cu²⁺(500 μg/L) produced significant DNA damages in THP-1 cells, and the actual effects on DNA damage were much worse than the theoretical combination effects of single contamination. This study indicated that either Cu²⁺ and polystyrene microplastics caused damage effect on DNA, showing a certain amount of genotoxicity, and the combination of the two had interactive enhancement damage effect on THP-1 cells.