BACKGROUND: Cough variant asthma (CVA) is a disease with no definitive diagnosis or pathogenic causes, and still lacks effective and safe treatment. Wuhu decoction is a traditional Chinese medicine with potential effects against CVA, of which underlying mechanism remains elusive. The aim of this study is to explore the therapeutic potential of Wuhu decoction against CVA. METHODS: The CVA mice model was established by ovalbumin (OVA) treatment. The airway hyperresponsiveness and remodeling were assessed. The pulmonary inflammatory injury was determined by counting of inflammatory cells and serum OVA-specific immunoglobulin E (IgE) in bronchoalveolar lavage fluid, as well as the amount of CD4 RESULTS: Wuhu decoction could improve airway hyperresponsiveness and remodeling in OVA-induced asthmatic mice model by regulating Th1/Th2 balance and affecting pulmonary inflammatory injury. On the molecular level, Wuhu decoction significantly inhibited the expression of lncTRPM2-AS, which was found to be a critical modulator of Th1/Th2 balance. Meanwhile, overexpression of lncTRPM2-AS could abolish Wuhu decoction-mediated protection effects on OVA-induced asthmatic mice model. CONCLUSIONS: This study discovered the protective function of Wuhu decoction against CVA and illustrated its molecular mechanism, highlighting the therapeutic application of Wuhu decoction for asthma treatment.