Quantum dots (QDs) have attracted great attention because of their favorable optical properties and have been widely applied in biomedical fields. However, in recent years, there have been an increasing number of reports about the cytotoxicity of QDs, especially cadmium-containing QDs, which may release cadmium ions to induce cytotoxicity. Importantly, the chemical composition and surface modifications of cadmium-based QDs determine the amount of Cd2+ released inside the cell. Thus, there is an urgent need for more systematic work to study the relationship between cytotoxicity and the surface properties of QDs. In this article, the cytotoxicity of seven cadmium-containing QDs with different constituent elements and surface chemistries are compared. The results show that the cytotoxicity of QDs is closely related to their constituent elements and surface properties: First, CdTe@ZnS core–shell QDs show much lower cytotoxicity than naked ones when they have similar surface modifications; second, the positively charged QDs are more toxic than the negatively charged ones. Moreover, both positively and negatively charged QDs without ZnS coatings lead to multipolar spindles, misaligned chromosomes, and G2/M checkpoint failures. Interestingly, although CdSe QDs with a PEG coating cause no apparent cytotoxicity in any of the cell lines studied, they can localize near the contractile ring during cytokinesis and then block contractile ring disassembly. The cellular effect of CdTe QDs comes not only from the release of cadmium ions but also the intracellular distribution of QD nanoparticles in cells and the associated nanoscale effects. It is also found that QD-caused cytokinesis failure is closely related to the decreased expression of Cyclin A and Cyclin B. Taken together, the above findings provide new insight into the dynamic fate of QDs during cell mitosis, and are important for understanding the intracellular effects of QDs on the mitotic spindle and chromosomes during cell division. Furthermore, this kind of cytotoxicity evaluation method should be applicable to studies of the biological effects and health impacts of other nanomaterials.