Hepatic tuberculosis (TB), which is secondary to post-hepatitis B cirrhosis, is extremely rare. We report the case of a 69-year-old man with post-hepatitis B cirrhosis complicated by primary isolated hepatic TB who was initially misdiagnosed as having hepatocellular carcinoma (HCC). The patient was hospitalized with complaints of 2 weeks of fever. He had a 20-year history of post-hepatitis B cirrhosis. The laboratory tests suggested that his serum alpha-fetoprotein (AFP) level was markedly elevated to 1210 ng/ml. From the abdominal ultrasound (US) and magnetic resonance imaging (MRI) images, we confirmed the presence of cirrhosis and discovered a space-occupying lesion of the hepatic left lobe as well as portal vein-filling defects. These results led us to consider primary liver cancer and portal vein tumor thrombus combined with decompensated cirrhosis. Biopsy and histology may be considered the ultimate diagnostic tests, but we excluded needle biopsy because of his high risk of bleeding, in addition, the patient declined the procedure. To cope with his fever, the patient was given broad-spectrum antibiotic treatment initially, followed by intravenous vancomycin. After antibiotic treatment had failed, the patient was treated with anti-TB for 10 days; after that, the patient maintained a normal temperature. The patient continued to receive tuberculostatic therapy for 6 months following his discharge. AFP completely returned to the normal level, and the aforementioned mass disappeared. Finally, hepatic TB secondary to post-hepatitis B cirrhosis with portal vein thrombosis (PVT) was considered to be the final diagnosis. More than two imaging techniques discover a space-occupying liver lesion and that the serum alpha-fetoprotein (AFP) level is extremely elevated, which means that hepatocellular carcinoma (HCC) could be diagnosed. However, some exceedingly rare diseases should not be excluded. This case illustrated that the non-invasive diagnostic criteria for liver cancer should be considered carefully when discovering a space-occupying liver lesion in a patient with cirrhosis and an elevated AFP level. In addition, primary hepatic TB should be considered and included in the differential diagnosis, and a biopsy should be performed promptly.