If atezolizumab–bevacizumab is not suitable for the patient, the choice of TKI treatment should consider clinical, radiological, and biological features: (i) tumour characteristics (number of tumours, vascular invasion, extrahepatic spread, and AFP level), (ii) underlying liver disease (CP score and portal hypertension), and (iii) general status (ECOG, comorbidities and symptoms associated with the disease). This evidence concerns the gene AFP and neoplasm.