A method for establishing an animal model of hepatocellular carcinoma (HCC) bone metastasis, the method including: 1) establishing 97H and LM3 cell clones with stable expression of firefly luciferase (LUC); 2) allowing HCC cells to form bone metastasis in nude mice via intratibial injection; 3) reproducing HCC bone metastasis in nude mice via intracardiac injection of tumor cells; and 4) isolating a sub-population of tumor cells that targets metastasis to bone. The 97H and the LM3 are highly metastatic HCC cell lines transfected with luciferase gene. BALB/cA-nu mice are 4-5 weeks old and maintained in laminar flow cabinets under SPF conditions and received human care throughout an entire study. A cell number for intratibial injection is 0.5×106, and a cell number for intracardiac injection is 1×106.