Tumor thrombus infiltration of hepatocellular carcinoma (HCC) into the inferior vena cava and right atrium is rare and is associated with a poor prognosis due to the critical location of the tumor and the limited efficiency of the available treatment strategies. In this study, we report the case of a patient with advanced HCC and tumor thrombus in the inferior vena cava and right atrium who demonstrated complete response with mass retraction upon Yttrium-90 trans-arterial radioembolization (90Y- TARE) therapy. Throughout the 16 months follow-ups after the radioembolization, the patient was free of any complications, revealing no occurrence of radiation-induced pneumonitis or tumor recurrence.