The purpose of this work is to present a body size and tube voltage dependent correction scheme for the Hounsfield Unit, HU, in medical X-ray Computed Tomography imaging. Boltzmann photon transport equation was employed to study X-ray interaction with bulk water in CT imaging. Experimentally measured X-ray output in body of phantoms and attenuation cross sections of water were employed in the derivation of beam intensity in X-ray imaging. A Somatom Emotion CT scanner from Siemens and electron density phantoms from CIRS were employed to acquire CT images of different body sizes and different tissue materials located at different depths from body’s surface. Tube voltage and depth dependent effective attenuation of bulk water was found from theoretical analysis in agreement with measured size-specific correction factors for CTDIvol under different tube voltages. A size and tube voltage dependent correction scheme for the Hounsfield Unit is established. For the same tissue material, body size has much larger impact on the CT number variations than that of depth from the body surface in phantom measurements. Good results were achieved by applying the established correction scheme on the experimentally measured CT number variations under different tube voltages and body sizes.