Mesoporous silica is of current interest for therapeutic applications, such as drug delivery, because of its small size and internal pore structure into which small molecules can be adsorbed. However, while the toxicity literature is extensive for micron-sized crystalline silica due to occupational health concerns, there is relatively little information available for mesoporous silica. Here, solid silica and mesoporous silica particles are characterized using SEM, DLS, XRD, and BET analysis; and their toxicities assessed using a modified MTT assay for cell viability and DPPP assay for lipid peroxidation. On a mass basis, mesoporous silica reduces cell viability from 82 ± 8% to 73 ± 16% compared to solid silica, likely due to the decreased density and therefore increased number of particles and particle surface area. This modest increase in toxicity, compared to the dramatic 600X increase in total surface area for mesoporous silica, from both pore and particle surfaces, suggests that the toxicity mechanism depends on the surface area available to the cell and not the total surface area. DPPP results support this conclusion and indicate that membrane lipid peroxidation is involved.