Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia.