Colloidal semiconductor nanoparticles (quantum dots, QDs) have attracted a lot of interests in numerous biological and medical applications due to their potent fluorescent properties. However, the possible toxic effects of quantum dots remain an issue of debate. In this study, we aimed to evaluate the cytocompatibility of bovine serum albumin (BSA) conjugated zinc oxide QDs for C2C12 cells. In the experiment, ZnO QDs were synthesized by using BSA as the structure directing agent, and the morphology and crystal phase of ZnO QDs were determined by transmission electron microscopy, X-ray diffractograms and Fourier transform infrared spectrograph techniques. The inverted fluorescence microscope results showed that ZnO QDs were distributed inside the cells. The toxicity of ZnO QDs was assessed by MTT methods, which revealed that ZnO QDs were highly cytocompatible in the concentration less than 200 μM. However, when the concentration of QDs was higher than 1000 μM ZnO QDs showed significantly toxicity, which was ascribed to generation of free zinc and formation of reactive oxygen species (ROS). Furthermore, the morphological observations exhibited that cells treated with ZnO QDs showed altered morphology, depolymerized cytoskeleton and irregular-shaped nuclei. This study provides helpful guidances on the future safe use and manipulation of QDs to make them suitable tools in nanomedicine.