One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.