Abstract: Objective To explore the expression of transforming growth factor β1 (TGF-β1) and Smad3 in children with asthma and the efficacy of vitamin D as an adjunct therapy in the treatment of pediatric asthma. Methods A total of 120 children with mild persistent asthma, who were treated at the Affiliated Hospital of Xuzhou Medical University from April 2022 to June 2023, were selected as an asthma group. Additionally, 80 healthy children undergoing physical examinations during the same period at the hospital were selected as a control group. The serum levels of TGF-β1 and Smad3 were compared between the two groups. According to the random number table method, the asthma group was divided into group A and group B (n=60). The serum levels of 25(OH)D, TGF-β1, Smad3, fractional exhaled nitric oxide (FeNO), lung function, frequency of respiratory infections, frequency of acute asthma exacerbations, and Childhood Asthma Control Test (C-ACT) scores were compared between groups A and B before treatment, and at 1 month and 3 months after treatment. Results The levels of TGF-β1 and Smad3 in the asthma group were significantly higher than those in the control group (P<0.05). After 3 months of treatment, group B showed a significant reduction in the frequency of respiratory infections and acute asthma exacerbations, and increased C-ACT scores compared with group A (P<0.05). At 1 month and 3 months after treatment, the levels of serum TGF-β1, Smad3, and FeNO in both groups decreased compared with those before treatment (P<0.05). The percentage of predicted forced expiratory volume in the first second (FEV1%), peak expiratory flow (PEF%), forced expiratory flow at 50% of forced vital capacity (FEF50%), forced expiratory flow at 75% of forced vital capacity (FEF75%), and maximum mid-expiratory flow (MMEF75/25%) increased compared with those before treatment (P<0.05), with greater improvements observed in group B than in group A (P<0.05). Conclusions The levels of serum TGF-β1 and Smad3 are significantly elevated in children with mild persistent asthma. The addition of vitamin D to standard inhaled corticosteroid treatment can reduce the expression of TGF-β1 and Smad3, decrease the frequency of acute asthma exacerbations, alleviate airway inflammation, and improve lung function, thereby enhancing clinical therapeutic efficacy.