ABSTRACT: The association of ABO blood group with prognosis of several malignancies has been established. However, its role in hepatocellular carcinoma (HCC) remains unclear.In this study, we investigated the prognostic role of ABO blood group in unresectable HCC patients receiving transarterial chemoembolization (TACE) as an initial treatment. Medical records of 2,611 HCC patients were collected, and clinical data of 282 unresectable HCC patients receiving TACE were ultimately analyzed retrospectively. A prognostic nomogram was generated for predicting 1-, 2-, and 3-year overall survival (OS) probability. A total of 114 (40.4%), 69 (24.5%), 64 (22.7%), and 35 (12.4%) HCC patients had blood groups O, A, B, and AB, respectively.The median OS times for patients with blood groups O, A, B, and AB were 24, 23, 20, and 20 months, respectively. Patients with blood group AB (hazard ratio [HR]=2.050, 95% confidence interval [CI], 1.331-3.157, P=0.001) or group non-O (HR=1.479, 95% CI, 1.110-1.972, P=0.008) had a poorer OS than those with blood group O. The prognostic nomogram, with a c-index of 0.701, was modest in predicting OS of unresectable HCC patients.Patients with non-O blood group, particularly blood group AB, had a worse OS compared with those having blood type O. ABO blood group can predict the prognosis in patients with unresectable HCC undergoing TACE as an initial therapy. Further external validation in larger cohorts is necessary to confirm their usefulness in clinical practice.