Objective To construct a highly metastatic human hepatocarcinoma cell line labeled with Luc ̄GFP, and to establish an orthotopic liver cancer model in nude mice that is convenient for observation and spontaneously metastatic. Methods The recombinant lentiviral expression vector pCDH ̄CMV ̄Luc ̄EF1 ̄GFP ̄Puro was constructed and transfected into the human hepatocarcinoma cell line HCCLM3. The naked body was constructed by intrahepatic injection of cell suspension into the left lobe of the liver or subcutaneous transplanted tumor tissue block intrahepatic implantation. Mouse orthotopic liver cancer model, using in vivo imaging technology and histopathology to compare the growth and metastasis of the two methods. Results A highly metastatic human hepatocarcinoma cell line HCCLM3 ̄Luc ̄GFP was constructed stably expressing luciferase (Luc) and green fluorescent protein (GFP). The results of nude mouse live imaging and pathology showed that the two methods established an orthotopic liver cancer model The tumor formation rate is 100%. The cell suspension method has a short modeling period and less damage to the host liver. It can better simulate the microenvironment of liver cancer patients and has a high metastasis rate. The tumor tissue mass method has a tumor size and location It is easier to control, but the transfer rate is lower. Conclusion The successful construction of Luc ̄GFP-labeled highly metastatic human hepatocarcinoma cell line HCCLM3 ̄Luc ̄GFP, cell suspension method and tumor tissue mass transfer method respectively established spontaneously metastatic and easy-to-observe orthotopic liver cancer models in nude mice, which are continuous , Intuitively monitor the growth and metastasis of tumors and lay the foundation for evaluating the efficacy of anti-liver cancer growth and metastasis drugs.