ObjectiveTo investigate the clinical characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC).MethodsClinical data of 177 patients who were diagnosed with cryptogenic HCC in the Third Afifliated Hospital of Sun Yat-sen University from January 2001 to December 2012 were analyzed retrospectively. The informed consents of all patients were obtained and the ethical committee approval was received. There were 138 males and 39 females with age ranging from 30 to 82 years old and median age of 56 years old. Data of clinical characteristics were collected and hepatitis B virus (HBV) serological markers were investigated. According to the different treatments, the patients were divided into surgical resection group (n=24), comprehensive treatment group (n=88), and conservative treatment group (n=65). Impacts of these 3 treatments on the survival of patients were compared.ResultsOf the 177 patients, the ratio of male to female was about 4:1. Patients with age over 60 accounted for 48.0% (85/177), liver cirrhosis 90.4% (160/177), non-alcoholic fatty liver disease (NAFLD) 19.2% (34/177), diabetes mellitus (DM) 21.5% (38/177). Patients with positive hepatitis B virus core antibody (HBcAb) accounted for 70.6% (125/177), alpha fetal protein (AFP) >400 μg/L 31.6% (56/177), liver function Child-Pugh grade A 62.7% (111/177), tumor diameter≤5 cm 35.6% (63/177), single tumor 54.2% (96/177), Barcelona Clinic Liver Cancer (BCLC) stage A 9.6% (17/177), stage B-D 90.4% (160/177). The 1-year survival rate was 92% in surgical resection group, 65% in comprehensive treatment group, but only 8% in conservative group.ConclusionsOccult HBV infection may be the main cause of cryptogenic HCC, though NAFLD and DM may also play an important role in its occurrence. Cryptogenic HCC most occurs on the basis of liver cirrhosis and is usually found at an middle or advanced stage during the initial diagnosis. The treatment outcomes and prognosis are poor so regular follow-up, early diagnosis are the key to improve the prognosis.