Objective: To investigate and analyze the efficacy of high-flow nasal cannula oxygen therapy in the sequential treatment of mechanical ventilation weaning for pneumonia complicated with type I respiratory failure. Methods: A total of 70 patients with pneumonia and type I respiratory failure admitted from January 2023 to December 2024 were divided into experimental group and control group. All patients were treated with mechanical ventilation. The experimental group was treated with high-flow nasal cannula oxygen therapy, and the control group was treated with non-invasive positive pressure ventilation. The clinical efficacy, blood gas analysis indexes (before treatment, 12, 24 and 48 hours after treatment) and sputum traits, inflammation index levels (before treatment and 3 days after treatment), sequential treatment time, total hospitalization time and reintubation mechanical ventilation rate were compared between the two groups. Results: The total effective rate of clinical efficacy in the experimental group was higher than that in the control group (P＜0.05). There were no statistically significant differences in PaO₂, PaCO₂, and SaO₂ levels between the two groups before treatment and at 12, 24, and 48 hours after treatment (P＞0.05). There was no significant difference in PaO₂, PaCO₂ and SaO₂ levels between the two groups before treatment and 12,24 and 48 hours after treatment (P＞0.05). There was no difference in CRP and PCT levels between the two groups before treatment (P＞0.05). After 3 days of treatment, CRP and PCT in the experimental group were lower than those in the control group (P＜0.05). There was no significant difference in sputum traits between the two groups before treatment (P＞0.05). After 12, 24 and 48 hours of treatment, the sputum traits I of the experimental group were better than those of the control group (P＜0.05). The sequential treatment time and total hospitalization time of the experimental group were lower than those of the control group (P＜0.05). Conclusion: High-flow nasal cannula oxygen therapy can improve the clinical efficacy of patients with pneumonia complicated with type I respiratory failure after mechanical ventilation weaning, dilute sputum, improve oxygenation, reduce inflammation, improve patient tolerance, reduce the risk of re-intubation mechanical ventilation due to intolerance, shorten the treatment time, and promote its rehabilitation. It is worthy of application.