Objective To explore the differences in clinical efficacy of different humidity regulation strategies of high-flow nasal cannula (HFNC) oxygen therapy in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with respiratory failure (RF). Methods A retrospective analysis was conducted on the clinical data of 92 elderly AECOPD patients with combined RF who visited 989 Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army from June 2023 to June 2025. According to different treatment plans, they were divided into group A and group B, with 46 cases in each group. Both groups were given HFNC treatment; the relative humidity was controlled at 60%-80% in group A and 81%-100% in group B. The oxygenation index (OI), respiratory rate (RR), heart rate (HR), sputum viscosity, comfort level and incidence of complications were compared between the two groups. Results After treatment, compared with group A, group B had higher OI (P＜0.05), sputum viscosity grade, and general comfort questionnaire (GCQ) scores (all P＜0.05), but lower RR and the incidence of complications (P＜0.05); there was no significant difference in HR between the two groups (P＞0.05). Conclusion HFNC relative humidity control at 81%-100% can improve oxygenation and RR in elderly AECOPD patients with RF, reduce sputum viscosity and complications, and improve patient comfort.