Multifocal hepatocellular carcinoma (MHCC) complicates the treatment strategy due to its high tumor heterogeneity. Global guidelines exhibit regional variations in defining surgical indications: Western guidelines prioritize liver transplantation for patients with MHCC meeting Milan criteria, while Asia-Pacific regions demonstrate greater preference for liver resection (LR), adopting more positive strategy even in intermediate-advanced stage patients (including those with higher tumor burden, compromised hepatic function, and inferior performance status). Recent studies have demonstrated that LR can significantly prolong survival in selected intermediate-advanced stage patients with MHCC. Advancements in minimally invasive techniques, conversion therapy, and comprehensive perioperative management have further expanded surgical indications for MHCC, with survival benefits undergoing qualitative improvements. In the future, the integration of multidisciplinary strategies combining surgical, locoregional, and systemic therapies will be essential for formulating personalized, precision-based, and standardized treatment protocols. Concurrently, progress in evidence-based medicine and technological innovation remains indispensable for optimizing long-term prognosis in patients with MHCC.