Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. Many researchers have investigated HCC at the level of genes, ribonucleic acid, proteins, cells, and animals. The resultant development of animal models and monitoring methods has improved the effectiveness of guidelines provided to researchers working with preclinical HCC models. HCC in animal models and clinical patients is monitored by various current imaging modalities such as ultrasound (US) imaging, computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET) and bioluminescence imaging (BLI). These techniques are currently used for both preclinical and clinical assessment, and provide valuable diagnostic information. In this article, we have mainly reviewed the established animal models and the assessment of orthotopic HCC using imaging modalities. Additionally, we have introduced a method of orthotopic HCC rat model developed in our laboratory. We have furthermore evaluated the occurrence of tumor mass using molecular imaging techniques.