Objective: To explore Non-invasive positive pressure ventilation (NIPPV) and High-flow nasel cannula oxygen therapy in patients with pneumonia induced expiratory failure. Mean arterial pressure (MAP) and Arterial partial pressure of oxygen (PaO2) under HFNC alternate therapy were studied. Methods: 129 patients with respiratory failure caused by pneumonia admitted to our hospital from March 2022 to February 2023 were selected as the study objects. Patients were divided into control group (n=64) and observation group (n=65) by random number table method. The control group was treated with NIPPV. Observation group was given alternating NIPPV and HFNC therapy. The hemodynamic parameters [Respiratory Rate (RR), heart rate (HR), MAP level] and ventilation status [PaO2, Partial pressure of carbon dioxide (PaCO2), Oxygen Saturation (SaO2)], inflammatory factor level [interleuin (IL-6), high-sensitive-C-reactive protein, necrosis factor-α (hs-CRP), Tumor necrosis factor-α (TNF-α)] and the occurrence of complications of the two groups were analyzed and compared. Results: After 2 h of treatment, the levels of RR, HR and MAP in both groups were significantly lower than before treatment, and the levels of RR, HR and MAP in observation group were significantly lower than those in control group (P<0.05). After 2 h of treatment, the levels of PaO2 and SaO2 in both groups were significantly higher than before treatment, and the levels of PaO2, SaO2 and PaCO2 in the observation group were significantly higher than those in the control group (P<0.05). After 2 h of treatment, PaCO2 levels in both groups were significantly lower than those before treatment, but there was no significant difference between the two groups (P>0.05). After 1 day of treatment, the levels of IL-6, hs-CRP and TNF-α in 2 groups were significantly lower than before treatment, and the levels of IL-6, hs-CRP and TNF-α in observation group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Conclusion: Alternating NIPPV and HFNC therapy can improve the hemodynamics and arterial blood gas indexes of patients with respiratory failure caused by pneumonia, and reduce the inflammatory response, with high safety.