Objective To compare the clinical efficacy and safety of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in treatment of acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19). Methods Sixty-eight patients with ARDS induced by COVID-19 in Wuhan Concorde Red Cross Hospital form January 25, 2020 to March 10, 2020 were included in the study. They were divided into an HFNC group (n=36) and an NIV group (n=36) according to the treatment. All patients received basic routine treatment, antiviral treatment and prevention therapy of secondary infection. The HFNC group received high-flow nasal cannula oxygen therapy, and the NIV group received NIV therapy. Then respiration and circulation parameters, comfort and tolerance, complications were compared between the two groups. Results After treatment for 3 days, 1 week, and 2 weeks in all patients with COVID-19 induced ARDS, respiratory rate (RR) was lower than that before therapy, arterial partial pressure of oxygen (PaO2), pulse oxygen saturation (SpO2), PaO2/FiO2 were higher than those before therapy (P<0.05), and therapeutic effect was time-dependent. But there was no significant difference of RR, PaO2, SpO2, PaO2/FiO2 between the HFNC group and the NIV group at different time points (P>0.05). After treatment for 2 weeks, the HFNC group patients' comfort, difficulty breathing, tolerance score were lower than the NIV group (P<0.05, P<0.01), the incidence rate of gastric distension and dry mouth etc. was lower than that in the NIV group (11.11% vs. 37.50%, P<0.05). There was no significant difference in rate of invasive mechanical ventilation or mortality between the two groups (P>0.05). Conclusions HFNC and NIV can improve respiratory and circulatory parameters of patients with COVID-19 induced ARDS. HFNC has better comfort and tolerance, and can reduce related complications.