A method and system for tumor ablation planning and guidance based on a patient-specific model of liver tumor ablation is disclosed. A patient-specific anatomical model of the liver and circulatory system of the liver is estimated from 3D medical image data of a patient. Blood flow in the liver and the circulatory system of the liver is simulated based on the patient-specific anatomical model. Heat diffusion due to ablation is simulated based on a virtual ablation probe position and the simulated blood flow in the liver and the venous system of the liver. Cellular necrosis in the liver is simulated based on the simulated heat diffusion. A visualization of a simulated necrosis region is generated and displayed to the user for decision making and optimal therapy planning and guidance.