Objective:To investigate the inhibitory effect on the orthotopic transplantation tumor model of human hepatocellular carcinomain using hydrodynamics-based transfection of recombinant retrovirus vector containg IκBα super repressor gene and its possible mechanism. Methods:The animal model of orthotopic transplantation tumor in nude mice was established with MHCC97-H and MHCC97-L cell lines. Tumor-bearing nude mice were divided into 4 groups:MHCC97-H group(control group),MHCC97-H+IκBαSR group(transfection group),MHCC97-L group(control group)and MHCC97-L+IκBαSR group(transfection group). After treatment for 7 days,plasmid pBABE-puro-IκBαSR and plasmid pBABE-puro in PBS solution were diluted according to the mouse weight. Plasmid pBABE-puro-IκBαSR and plasmid pBABE-puro were respectively transferred into transfection group and control group via the tail vein by hydrodynamic injection. The survival rate of nude mice bearing the tumor was observed. The size,weight and volume of tumor in situ and the number of metastatic tumor in liver were examined,and the inhibitory rates of tumor growth were calculated. ALT and AST in sera were observed. Immunohistochemistry was used to detect the expression of NF-κB in liver cancer tissue. IκBα was determined with western blot. Results:Plasmid pBABE-puro-IκBαSR significantly promoted the survival rate and inhibited the level of ALT and AST in transfection groups than in control groups. In transfection groups,the tumors were significantly smaller and lighter than those in control groups,and the inhibition rates were 29.3% and 33.0% respectively. In cellular nucleus of the transfection groups,the expression levels of NF-κB p65 and IκBα were higher than the control groups. Conclusion:Hydrodynamics-based transfection of plasimd pBABE-puro-IκBαSR gene to the orthotopic implant model of human hepatocellular carcinoma can inhibit the tumor. Its mechanism may be that the transfected IκBαSR gene suppress the activation of NF-κB signaling in cancer cells.