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Recent advances in systemic therapy have had major impacts on treatment strategies for hepatocellular carcinoma (HCC). The 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines incorporate a new section on clinical decision-making for personalized medicine, although the first treatment suggested by the BCLC guidelines is based on solid scientific evidence. More than ever before, the appropriate treatment strategy must be selected prior to the initiation of therapy for HCC. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) is essential for liver imaging and the hepatobiliary phase (HBP) of EOB-MRI reflects the expression of organic anion transporting polypeptide (OATP) transporters. Molecules associated with OATP expression are relevant in the molecular classification of HCC subclasses, and EOB-MRI is becoming increasingly important with advances in the molecular and genetic understanding of HCC. In this review, we describe imaging findings for the pretreatment prediction of response to standard therapies for HCC based on the BCLC algorithm using the HBP of EOB-MRI, with specific attention to the molecular background of OATPs. A more complete understanding of these findings will help radiologists suggest appropriate treatments and clinical follow-ups and could lead to the development of more personalized treatment strategies in the future. Clinical relevance statement: In the coming era of personalized medicine, HBP of EOB-MRI reflecting molecular and pathological factors could play a predictive role in the therapeutic efficacy of HCC and contribute to treatment selection. Key Points: • Imaging features of hepatobiliary phase predict treatment efficacy prior to therapy and contribute to treatment choice. • Wnt/β-catenin activation associated with organic anion transporting polypeptide expression is involved in the tumor immune microenvironment and chemo-responsiveness. • Peritumoral hypointensity of hepatobiliary phase reflecting microvascular invasion affects the therapeutic efficacy of locoregional to systemic therapy. [ABSTRACT FROM AUTHOR]