Spontaneous regression (SR) of malignant tumors is defined as the partial or complete reduction of a tumor without medical intervention. This unusual phenomenon has been reported in various types of malignancies. We present a rare case of a 73-year-old woman with untreated chronic hepatitis C who was diagnosed with extensively diffused hepatocellular carcinoma (HCC) accompanied by a tumor thrombus in the left branch of the portal vein. Remarkably, extensive tumor regression occurred under palliative care. This case highlights the potential mechanisms responsible for SR of HCC, including tumor hypoxia, immune activation, and systemic inflammatory responses, and emphasizes the need for further research to clarify these mechanisms.