Obstructive sleep apnea hypopnea syndrome (OSAHS) is characterized by the aggravation of upper airway constriction or obstruction, and it is associated with high incidence of various metabolic diseases and high mortality. Continuous positive airway pressure (CPAP) is now recommended as the first-line therapy for OSAHS, but its application is limited by its unsatisfactory patient tolerance. Previous studies have showed that high flow nasal cannula (HFNC) may improve symptoms in some patients with OSAHS. Therefore, the aim of the present study was to evaluate the effect of HFNC on OSAHS in a larger cohort than in previous research and to study the details of its therapeutic characteristics.Polysomnography recording with and without HFNC was performed in 56 OSAHS patients with a wide spectrum of disease severity. Subgroups were divided by different treatment response criteria to identify the effect of this device.Of 56 patients enrolled, 9 were of mild severity (AHI, 5 to <15 events/h), 30 were of moderate severity (AHI, 15 to <30 events/h), and 17 patients were severe (AHI ≥ 30 events/h); 34 patients were younger than 50 years old and 22 patients were older than 50 years old. AHI decreased significantly (from 26.9 ± 14.7 to 21.5 ± 17.0 events/h, p < 0.001) after HFNC treatment in general. The subjects of responder group accounted for 21%. There was a negative correlation between the difference of AI and the difference of HI in nonresponder group before and after HFNC treatment, and the negative correlation was strong (Pearson's test, r =  - 0.804, p = 0.000). Of the patients with mild to moderate severity, 76% achieved any AHI reduction and 24% of patients achieved at least 50% reduction in AHI. Older patients (the age of responder group 52.6 ± 11.7 vs. nonresponder group 43.7 ± 12.1 years old, p < 0.05), especially patients older than 50 years, had a better response rate (≤ 50 years 9% vs. > 50 years 41%, p = 0.007).HFNC may be useful in treating patients with OSAHS, especially older patients and those with mild to moderate severity. HFNC may be an alternative treatment when patients are intolerant of CPAP.© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.