Objective: To investigate the effect of azithromycin sequential therapy combined with Xiaoer Feireqing granule on mycoplasma pneumoniae pneumonia in children. Methods: 82 children with mycoplasma pneumoniae pneumonia admitted to our hospital from December 2022 to December 2024 were selected as the study objects. According to random number table method, the children were divided into control group and observation group, with 41 cases in each group. The control group was treated with azithromycin sequential therapy. Observation group was treated with Xiaoer Feireqing granule on the basis of control group. The clinical efficacy, lung function [forced vital capacity, maximum expiratory peak flow rate, forced expiratory volume level in the first second], immune function [immunoglobulin A, immunoglobulin G, immunoglobulin M levels], inflammatory factors [C-reactive protein, tumor necrosis fact-α, interleukin-6] levels and the occurrence of adverse reactions were analyzed and compared between the two groups. Results: The total effective rate of observation group was significantly higher than that of control group (P < 0.05). After 3 courses of treatment, the levels of forced vital capacity, maximum peak expiratory flow rate and forced expiratory volume at the first second of both groups were significantly higher than before treatment, and the levels of forced vital capacity, maximum peak expiratory flow rate and forced expiratory volume at the first second of the observation group were significantly higher than the control group (P < 0.05). After 3 courses of treatment, the levels of serum immunoglobulin A, immunoglobulin G and immunoglobulin M in 2 groups were significantly higher than before treatment, and the levels of serum immunoglobulin A, immunoglobulin G and immunoglobulin M in observation group were significantly higher than those in control group (P < 0.05). After 3 courses of treatment, the levels of serum C-reactive protein, tumor necrosis factor-α and interleukin-6 in 2 groups were significantly lower than before treatment, and the levels of serum C-reactive protein, tumor necrosis factor-α and interleukin-6 in observation group were significantly lower than those in control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion: Azithromycin sequential therapy combined with Xiaoer Feireqing granules can improve the therapeutic effect, reduce the level of inflammatory factors, improve the immune function and lung function indexes in children with mycoplasma pneumoniae pneumonia, and have high safety.