The penetration and transportation of nanoparticles (NPs) inside the cancer cells is critical to study. In this article, cancer cells (HCT-116) were treated with functionalized magnetic NPs for the period of 48 hr and studied their ultrastructure by transmission electron microscopy (TEM).The NPs-treated cells were prepared by chemical fixation and sliced into electron-transparent arbitrary sections (200 × 200 μm 2 ) by ultramicrotome. Major events of NPs-cell interaction, such as penetration of NPs, encapsulation of NPs into the intracellular compartments, transportation of NPs, and NPs exit, were examined by TEM to understand the mechanism of cell death. The NPs showed the uniform spherical shape with broad size distribution (100-400 nm), while cells displayed irregular morphology with average diameter~5 μm. Our results showed the successful penetration of NPs deep into the cell, encapsulation, transportation, and exocytosis. Furthermore, we tested the different concentrations (0, 1.5, 12.5, and 50 μg/ml) of NPs on cancer cells and evaluated the cell viability. Laser confocal microscopy and colorimetric analysis together demonstrated that the cell viability is a dose-dependent phenomenon, where 50 μg/ml specimen showed the highest killing of cancer cells compared to other dosages. K E Y W O R D S arbitrary sections, cancer cells, magnetic nanoparticles, nanoparticle-cell interaction, TEM