Objective To investigate the difference between BALB/ c mutant curly mice and normal BALB/ c mice in the establishment of tumor models by hepatic portal vein injection and establish a quantitative analysis method of images using Image J software. Methods H₂₂ cells were injected into the liver through the portal vein of the two groups and livers were removed 21 days later. The largest diffuse lesion of the liver lobe was selected for analysis. The vertical view of the tumor appearance was obtained by acquiring images, and then Image J software was used for quantitative analysis and comparison of liver tumor images. Results Multiple diffuse tumors were found in both groups. The multiple and diffuse degree of tumors in the curly mice group was significantly higher than that in the normal mice group, and the tumors in curly mice group were more closely related to the surrounding normal liver tissue infiltration than that in normal mice group. The result of Image J software analysis showed that there was no significant difference between the two groups, but the proportions of tumors and tumors in the liver of curly mice were significantly higher than those in normal mice (P<0.01). Conclusions The animal model of advanced liver tumors was established successfully. The ability of BALB/ c mutant curly mice to model tumor cells via portal vein injection was significantly better than that of normal BALB/ c mice. Moreover, a quantitative analysis method of images was established using Image J software.