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Background: Transarterial chemoembolization (TACE) is recommended as a palliative treatment for patients of the B stage of the Barcelona Clinic Liver Cancer (BCLC) classification. Aims: To identify clinical, biological, and radiological predictors of survival in patients undergoing TACE and develop a pre-therapeutic prognostic score. Methods: 191 adult cirrhotic patients treated for HCC with TACE at the University Hospital (UH) of Clermont-Ferrand (France) from 2007–2017 were retrospectively included. We investigated the impact of baseline liver function, patient characteristics, and tumor burden on overall survival and developed a prognostic score. Results: Patients had a median age of 66 years and 126 patients were Child A. The AFP-DIAM score distinguishes two groups with a significant difference in survival time (median OS 28.3 months in patients with a score = 0 versus 17.7 months in patients with a score > 0). AFP-DIAM was validated on an external cohort, is well calibrated, and has the best discrimination capacity (C-index) as compared to NIACE, HAP, STATE, and SIX TO TWELVE. AFP-DIAM and SIX TO TWELVE are the more easy-to-use scores. When AFP-DIAM and the SIX TO TWELVE scores were tested in the same statistical model, results confirmed a better AFP-DIAM performance. Conclusions: The AFP-DIAM is an easy-to-use score which allows to distinguish two groups with different prognosis before the first TACE session. Its use could provide further support to BCLC system to guide the therapeutic strategy of patients with HCC. An easy-to-use score allows to distinguish two groups with a different median survival. Patient with a high score could receive immunotherapy as first-line treatment. [ABSTRACT FROM AUTHOR]