Objective To explore the efficacy of ceftazidime-avibactam sodium combined with moxifloxacin in the treatment of hospital-acquired pneumonia (HAP). Methods A total of 68 patients with HAP admitted to the Binhai People""s Hospital from June 2022 to December 2024 were selected as the study subjects. According to the treatment regimen, they were divided into a combination group and a control group. The pneumonia severity index (PSI) scores, modified Medical Research Council dyspnea scale (mMRC) scores, time for clinical symptoms to return to normal, adverse reactions, and blood gas analysis [arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), arterial blood oxygen saturation (SaO2)] and inflammatory indicators [soluble intercellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), cysteinyl leukotrienes (CysLTs)] before and after treatment were compared between the two groups. Results The time to normalization of cough, body temperature, and pulmonary moist rales in the combination group were all shorter than those in the control group (all P＜0.05). After treatment, the PSI scores and mMRC scores in both groups were lower than before treatment, and the scores in the combination group were lower than those in the control group (P＜0.05). After treatment, PaCO2 in both groups was lower than before treatment, while PaO2 and SaO2 were higher than before treatment, with the combination group showing greater improvement than the control group (P＜0.05). After treatment, the levels of sICAM-1, CRP, and CysLTs in both groups were lower than before treatment, and the decrease in the combination group was greater than that in the control group (all P＜0.05). During treatment, there was no statistically significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion The combination therapy of CAZ and moxifloxacin demonstrates definite clinical efficacy in the treatment of patients with HAP, outperforming monotherapy with CAZ. It effectively promotes the resolution of symptoms and alleviates inflammatory responses.