A series of MCM-41-type mesoporous silica nanoparticle (MSN) materials with different morphologies (spherical and tubular) and sizes but similar surface and pore properties were synthesized and characterized. The effect of particle morphology on human red blood cell (RBC) membrane integrity was evaluated using flow cytometry, UV-Vis spectroscopy, confocal fluorescence and electron microscopy. Although the hemolytic activity was miniscule at higher nanoparticle concentrations for MSN with spherical geometry (up to 500 μg mL⁻¹), electron microscopy results showed significant occurrences of RBC spiculation, indicating damage to the plasma membrane. However, no evidence for particle embedment or internalization was found in all the geometries and particle concentrations tested. We envisage that complete hemocompatibility studies of varied nanoparticle morphologies would provide important guidelines when considering the overall toxicity of these nanodevices in vivo.