Nanodiamonds (NDs) possess many excellent physical and chemical properties that make them attractive materials for applications in biomedicine. In this paper, the adsorption and delivery of a large amount of sodium ions into the cell interior by NDs in serum-free medium is demonstrated. The excess sodium ions inside the cells induce osmotic stresses followed by cell swelling and an increase in the intracellular levels of calcium and reactive oxygen species (ROS), which leads to severe cellular damage. In complete culture medium, however, serum proteins wrapped around the NDs effectively prevent the sodium ions from adsorbing onto the NDs, and thus the NDs show no cytotoxicity. This work is the first to elaborate on the correlation between the sodium ions adsorbed on the nanomaterials and their bio-effects. Excessive ions delivered into cells by NDs might have potential applications in tumor therapy.