Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, we investigate the biological network and signaling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, we confirmed the correlation between XQLD and asthma, and we screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping “Childhood asthma-related genes” of DisGeNET database, we identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction (PPI) and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GO enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of KEGG signaling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum IFN-γ expression, and downregulated serum IL-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating IL-6/STAT3 signaling pathway.