Amebic liver abscess and hepatocellular carcinoma have similar clinical manifestations. Early amebic liver abscess can be misdiagnosed as hepatocellular carcinoma, but it can often be differentiated by auxiliary examination. Amebic liver abscess is a complication of intestinal amebic infection, which mostly manifests as right upper abdominal pain, fever, liver enlargement and tenderness. If typical pus (brownish-brown color) is obtained by hepatic puncture, or amebic trophozoites are found in the pus, or the treatment of specific anti-amoebic drugs has a good effect on the amebic abscess, the diagnosis can be confirmed as amebic liver abscess. Hepatocellular carcinoma also mostly manifests as pain in liver area, liver enlargement and fever, but the degree of fever is lower than that of amebic abscess, and the symptoms usually worsen progressively, and the application of amoebic drug treatment is ineffective. Clinical tests such as alpha-fetoprotein measurement, liver ultrasonography, abdominal CT, radionuclide liver scanning, selective hepatic arteriography, and magnetic resonance imaging can be used to make a clear diagnosis. Liver puncture and anti-amoebic drug treatment test are also helpful for differentiation, and the patient’s past medical history is also a very important reference.