Magnetic particles (MPs) of nano_{micron-scale have been widely used in biomedical applications and laboratory research. It is vital to evaluate the performance and influence of MPs incubated with cells. This study aimed to test the cytotoxicity of core-shell polystyrene magnetic beads and explore the related mechanisms for further use in cartilage regeneration. Core-shell polystyrene magnetic beads at 0-2 ng}cell were incubated with human chondrocyte cell line C28/I2 for five days. Cell viability, proliferation, morphology and expression of key genes that regulate the cell function were evaluated. The results were compromised in a dose- and time-dependent way. There were visible cytotoxic effects at a high loaded dose of 2 ng/cell, such as cell uptake, low viability, slow proliferation rate and poor cell morphology. Gene expression was a balanced consequence between toxic factors and cell repair performances. Core-shell polystyrene magnetic beads showed acceptable biocompatibility except at higher doses (over 2 ng/cell) where low cytotoxicity was apparent. These interferences were probably owing to ROS (reactive oxygen species) generation, cytoskeleton architecture rearrangement, iron imbalance, modification detachment, etc.