Gold nanoparticles (GNPs) were demonstrated as X-ray imaging contrast agents and radiosensitizers in mice. However, the translational medical applications of GNPs in to the clinical practice need further detailed information on the biological effects related to the enhanced doses in malignant and healthy cells. The idea of improving radiotherapy with high atomic number materials, especially gold foils, was initiated in our research unit in the 1980s. Recently, experimental and theoretical efforts were made to investigate the potential improvement of imaging and radiotherapy with GNPs. Initially, the present work attempts to validate the dose enhancement effects of GNPs to cancer cells; secondly, it intends to examine the possible side effects on healthy cells when using GNPs as X-ray contrast agent. In this study, three Monte Carlo simulation programs, namely PENELOPE-2011, GEANT4 and EGSnrc were used to simulate the local energy deposition and the resulting dose enhancement of GNPs. Diameters of the GNPs were assumed to be 2 nm, 15 nm, 50 nm, 100 nm and 200 nm. The X-ray energy spectra for irradiation were 60 kVp, 80 kVp, 100 kVp, 150 kVp with a filtering of 2.7 mm Al for projectional radiography, and 8 mm Al for 100 kVp and 150 kVp for computed tomography. Additional peak energy of 200 kVp was simulated for radiotherapy purpose. The information of energy deposition and dose enhancement can help understanding the physical processes of medical imaging and the implication of nanoparticles in radiotherapy.