Silver nanoparticles (AgNPs) are being increasingly used in commercial products (e.g., cosmetics, textiles, and food containers) due to their antimicrobial activities, and thus, more information is needed on their toxicologic properties. In this study, we investigated the toxic effects of AgNPs (7.5, 30, and 60 nm) in combination with manganese (II) chloride or zinc sulfate. The sizes and morphologies of AgNPs were characterized by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy. For cytotoxicity evaluations, MTT assays were conducted using the human carcinoma cell lines (A375p, A549, HepG2, and ACHN). In addition, MnCl₂ or ZnSO₄ was co-treated with AgNPs to determine whether the toxicities of the AgNPs were modified. Intracellular reactive oxygen species (ROS) generation and oxidative stress were determined using a DCF-DA assay, a GSH assay, and a catalase assay. Cell cycle analysis was carried out using flow cytometry and propidium iodide (PI) staining. The genotoxicity of AgNPs was evaluated using a chromosomal aberration test and CHL/IU cells. MTT assays showed that 7.5 nm AgNPs were more toxic to the human carcinoma cell lines than 30 or 60 nm AgNPs, and that 30 nm AgNPs were more toxic than 60 nm AgNPs. Cell viability after treatment with AgNPs was lower for HepG2 cells than the other cell lines. In terms of manganese co-exposure, the cytotoxicity of AgNPs was increased in all four cancer cell lines examined. However, its cytotoxicity was decreased in the presence of zinc in the A375p and HepG2 cell lines. ROS levels and oxidative stress were increased in A375p cells by AgNPs, and oxidative stress induced by AgNPs was increased in the presence of manganese, but decreased in the presence of zinc. Cell cycle delays in the S and G2/M phases were observed in A375p cells treated with AgNPs, but these delays were ameliorated by manganese and zinc. In the chromosomal aberration test, AgNPs induced numerical chromosome aberration and endoreduplication, and these were prevented by zinc and by manganese. Furthermore, the depletion rates of tubulin treated with AgNPs were lower than in controls. In addition, the addition of Mn or Zn to tubulin treated with AgNPs restored tubulin depletion rates to control levels. This study shows that the toxicity of AgNPs is due to the induction of oxidative stress and depleted tubulin following cell cycle changes. Furthermore, these toxic effects appeared to be reduced by zinc but not by manganese due to their effects on ROS generation.