The harm of microplastics (MPs) to aquatic ecosystems is caused by their stable and non-degradable properties. Additionally, the pollutants such as heavy metals in the water are easy to be adsorbed on their surface with their small particle size and large specific surface area, resulting in environmental pollution. Therefore, the study on the mixture toxicity of MPs and heavy metals has theoretical significance for the risk assessment of aquatic ecosystems. In the present study, 10 nm polystyrene (PS) and cadmium (Cd) were used, and their individual and mixture acute toxicities on grass carp (Ctenopharyngodon idellus) were examined. The results indicated that the mortality of the fish increased with the concentration from 10 mg L⁻¹ to 20 mg L⁻¹, and the existence of PS-MPs elevated the Cd concentrations in the fish and accelerated the death. Whether the Cd and/or the PS-MPs concentrations caused varying degrees of damage to the gills, kidney, liver, and muscles of the grass carp, especially under the highest concentrations (20 mg L⁻¹ Cd + 300 μg L⁻¹ PS-MPs). Moreover, low concentrations of PS-MPs alone (30 μg L⁻¹ PS-MPs) significantly increased the superoxide dismutase (SOD) activity in the kidney and liver, reaching 12.43% and 14.38%, respectively (P < 0.05). The peroxidase (POD) activity was increased only in the kidney, up to 25.95% (P < 0.05). Also, significant reductions in SOD and POD activities were observed in the combination of high concentration of Cd (20 mg L⁻¹) and 300 μg L⁻¹ PS-MPs (P < 0.05). To the best of our knowledge, there are few studies on the impact of combined toxicity of PS-MPs and Cd on grass carp under laboratory conditions. Therefore, these findings may provide a theoretical guarantee for pollution prevention and control in the aquatic ecosystem.