Objective: To investigate the diagnosis and treatment of hepatocellular carcinoma (HCC) with fever as main symptom. Methods: The clinical data of 10 HCC patients with fever as main symptom recently admitted to our hospital were retrospectively analyzed. Results: Of the 10 patients, 4 cases were diagnosed with HCC, but 6 cases had been misdiagnosed as liver abscess by other hospitals and were given anti-infective treatment for a long time. All of the patients received aggressive management and their temperatures were effectively controlled after admission. Six patients underwent transcatheter arterial chemoembolization (TACE) and 4 patients underwent surgical treatment. One patient died 2 weeks after surgery. The follow-up data suggested a poor general prognosis. The other 9 cases died between 2 months and 1 year after treatment. Conclusion: HCC with fever as main symptom should be differentiated from liver abscess, and surgical resection is the first choice for treatment of these patients.