〔Abstract〕 Objective To explore the clinical effect of Montelukast sodium combined with Zhisou San in the treatment of chronic cough in children. Methods 80 children with chronic cough from Anyang Hospital of Traditional Chinese Medicine from October 2021 to August 2023 were selected as the study objects, and randomly divided into control group and observation group, with 40 cases in each group. The control group was treated with montelukast sodium, and the observation group was treated with Zhisou San on the basis of the control group. The clinical efficacy, pulmonary ventilation index, inflammatory factor level and immune function of the two groups were compared. Results The total effective rate of observation group was 90.00%, higher than that of control group 72.50%, the difference was statistically significant (P < 0.05). Forced vital capacity (FVC), maximum expiratory flow (PEF) and forced expiratory volume at the first second (FEV1) in observation group were higher than those in control group one month after treatment, and the differences were statistically significant (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), procalcitonin gene-related peptide (CGRP) and eosinophilic cationic protein (ECP) in the observation group were lower than those in the control group after 1 month of treatment, and the differences were statistically significant (P < 0.05). The levels of peripheral blood of differentiation antigen (CD)4⁺ , CD3⁺ and CD4⁺ /CD8⁺ in the observation group were higher than those in the control group after 1 month of treatment, and the differences were statistically significant (P < 0.05). Conclusion Montelukast sodium combined with Zhisou San can reduce the level of inflammatory factors, regulate immune function, improve pulmonary ventilation index and improve clinical efficacy in children with chronic cough.