Objective To construct an intrahepatic model of advanced liver cancer (hepatocellular carcinoma, colorectal cancer liver metastasis, breast cancer liver metastasis, non?small cell lung cancer liver metastasis) by injecting cancer cells through the hepatic portal vein. Methods MHCC97?H, a highly aggressive cell line of hepatocellular carcinoma; SW480, a metastatic colorectal cancer cell line; MDA?MB?231, a human triple?negative breast cancer cell line; or A549, a non?small cell lung cancer cell line, was cultured and seeded into the liver of BALB/ c nude mice by injecting cancer cells through the hepatic portal vein. After 3 - 4 weeks of growth, mice were analyzed by PET/ CT screening. Mice were injected with approximately 200 μCi nuclide probe18 F?FDG through the tail vein. The BALB/ c nude mice were analyzed by PET/ CT screening after 30 -40 min. The mice were then collected, and their livers were obtained and photographed to determine the presence of tumor nodules on the liver of BALB/ c nude mice. Results MHCC97?H, A549, SW480, or MDA?MB?231 cells grew and multiple diffuse tumor nodules formed in the nude mouse livers. Nodules in the nude mouse livers formed by cancer cells could be identified by PET/ CT screening; the PET/ CT intensity of nodules formed after A549, SW480, or MDA?MB?231 cell injection was weaker than that of MHCC97?H cells. Conclusions An intrahepatic tumor animal model of advanced liver cancer has been successfully constructed by injecting cancer cells through the hepatic portal vein. This is a promising model for research on liver cancer or antitumor drugs.