An 83-year-old man was admitted with a chief complaint of exacerbation of dyspnea. His blood oxygen saturation was 90% in the recumbent position despite oxygen therapy, and it dropped to less than 80% when the patient attempted to sit upright. A computed tomography scan revealed a giant hepatic cyst compressing the right atrium and the inferior vena cava. After percutaneous drainage, the oxygen saturation improved and did not change with alteration of the patient's positions from recumbent to sitting or standing. This case report describes a patient with the platypnea-orthodeoxia syndrome due to a giant hepatic cyst successfully managed by percutaneous drainage.