Objective To observe the efficacy and safety of Xuanfei Huatan Sanyu Decoction combined with acetylcysteine in the treatment of children with bronchiolitis. Methods 94 children with bronchiolitis diagnosed and treated in our hospital from September 2021 to September 2023 were selected as the study objects. The children were randomly divided into control group and observation group, with 47 cases in each group. The control group was treated with acetylcysteine. Observation group was treated with Xuanfei Huatan Sanyu Decoction combined with acetylcysteine. The clinical efficacy, duration of clinical symptoms and arterial blood gas analysis indexes [PaCO2, pH, SpO2], inflammatory response [ECP, EOS, IL-4, IFN-γ], immune function (CD3+, CD4+, CD8+), and the occurrence of adverse reactions of the two groups were analyzed and compared. Results The total effective rate of observation group was significantly higher than that of control group (P < 0.05). The disappearance time of asthma, cough, wheezing sound and pulmonary rales in the observation group was significantly shorter than that in the control group (P < 0.05). After treatment, PaCO2 decreased, pH and SpO2 increased in both groups. After treatment, PaCO2 was significantly decreased, pH and SpO2 were significantly increased in the observation group (P < 0.05). Compared with before treatment, the serum ECP, EOS, IL-4 and IFN-γ levels of the two groups were decreased after treatment, and the serum ECP, EOS, IL-4 and IFN-γ levels of the observation group were significantly lower than those of the control group (P < 0.05). Compared with before treatment, CD3+ and CD4+ increased and CD8+ decreased in both groups after treatment. After treatment, CD3+ and CD4+ were significantly increased, while CD8+ was significantly decreased in observation group (P < 0.05). There were no significant differences in adverse reactions between the two groups (P > 0.05). Conclusion Xuanfei Huatan Sanyu Decoction combined with acetylcysteine in the treatment of children with bronchiolitis can improve the curative effect, promote the recovery of the disease, improve the arterial blood gas, reduce the inflammatory state of the body, improve the immune function, and has certain safety.