Nanoparticles (NPs) with high-Z atoms have been widely studied as radiosensitizers for use in cancer therapy. Over the past few years, the application of FePt NPs has attracted extensive research interest. Promising results have been obtained, yet limited knowledge is available regarding its potential use as a radiosensitizer. The goal of this study is to investigate the radiosensitiza-tion capability of FePt nanoparticle clusters (NPCs) under the exposure of kilovoltage photons using Monte Carlo simulation. First, in order to obtain a realistic distribution of NPCs on the microscopic level, Hela cells were incu-bated with FePt NPs, and the distribution of NPCs was obtained by optical microscope images and X-ray Nano-CT experiments. Based on these images, a simplified cellmodel was developed to evaluate the DER of two material types (FePt and FePt3). For each type, the dependence of DER on the thickness and angular distribution of NPCs on the surface of the cell membrane was studied quantita-tively. Our results suggest that DER is strongly dependent on photon energy and the distance from the NPCs to the nucleus. Fe1Pt3 is able to achieve a higher DER relative to Fe1Pt1. For a given X-ray energy, DER demonstrates an initial increase to a maximum value but gradually saturates as the thickness of NPCs increases from 250 up to 2000 nm due to a trapping effect. The impact on DER resulting from the coexistence of the NPCs on the cell membrane and the nuclear membrane was also investigated.