The COVID-19 outbreak has become a global pandemic within only a few months. COVID-19 patients complicated with severe hypoxemia usually required high-flow nasal cannula (HFNC) and mechanical ventilation. Prone positioning is a salvage therapy for refractory hypoxemia and has proven to be effective in increasing tidal volume and improving oxygenation and diaphragmatic function in patients with acute respiratory distress syndrome (ARDS) (1-3). However, all these studies were conducted in intubated patients. A recent study revealed that early application of prone positioning with the HFNC might avoid the need for intubation in moderate to severe ARDS patients (4), suggesting that the benefits of prone positioning also exists in the non-intubated patients (5). Also, endotracheal intubation may carry high nosocomial infection risk for the physicians who perform this procedure. Avoiding intubation could also be protective of them. Based on these potential beneficial effects, we conducted a pilot study and reviewed our preliminary experience of prone positioning in HFNC to treat COVID-19 who were complicated with severe hypoxemia.