Primary liver cancer is a common malignant tumor in China. The current main treatment methods include surgical resection, liver transplantation, interventional therapy, radiofrequency ablation, chemotherapy, targeted therapy, and immunotherapy. Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT) represents a critical treatment option for converting unresectable intermediate to advanced hepatocellular carcinoma. This report details a case of a patient with a giant hepatocellular carcinoma in the right lobe treated with ⁹⁰Y resin microsphere at the Third Affiliated Hospital of Sun Yat-sen University. Post-treatment, the tumor showed significant necrosis and reduction in size, with a marked decrease in alpha fetoprotein (AFP) levels and notable improvement in clinical symptoms. The case highlights the substantial efficacy of ⁹⁰Y-SIRT in controlling tumor progression and enhancing patient quality of life.