Background：Wheezing is an important respiratory symptom in the diagnosis of asthma. However, wheezing is common in children and often related to viral infection. This and the lack of reliable biological indicators for asthma create difficulty in diagnosing asthma early in children. Objective: In this study, the levels of CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children with different diagnostic outcomes were investigated to determine correlation with a diagnosis of asthma and to assess their potential clinical value as a biological indicator for this disease. Methods: A prospective study was performed with a cohort of wheezing children aged 3 months to 6 years hospitalized in the Division of Pulmonary Pediatrics at Shanghai Xinhua hospital and Shanghai children’s medical center affiliated to Shanghai Jiao Tong University School of Medicine from July 2017 to March 2018. After inclusion, the level of serum IgE, presence of allergen-specific serum IgE (sIgE) and proportion of circulating CD4+CCR6+CRTh2+ memory Th2 cells were counted. In addition, the patients’ personal and family histories of allergic disease were acquired by questionnaire. The children were followed up annually over 2 years by telephone call with a guardian to record whether the child had been diagnosed with asthma. The accuracy of an increased proportion of CD4+CCR6+CRTh2+ memory Th2 cells as an indicator of asthma was assessed. Results: A total of 43 children completed follow-up. The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children diagnosed with or without asthma was 1.2%(0.8%~2.9%) and 0.6%(0.1%~0.9%), respectively, and was significantly higher in children diagnosed with asthma (P<0.01). The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in atopic children was also significantly higher in children diagnosed with asthma than in children without asthma, at 1.3%(0.8%~2.9%) and 0.6%(0.3%~1.0%), respectively, (P<0.01). Furthermore, the level of serum IgE was significantly higher in children with asthma (P<0.05). Logistic regression analysis indicated that the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells were independent risk factors for asthma. The area under the receiver operating characteristic curve (ROC) was 0.922. There was no significant difference in the positive rate of memory Th2 cells in the context of allergic rhinitis (AR) or atopic dermatitis (AD) (P>0.05). Conclusion: Our exploratory study found that an increase in the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells could be used as a biological indicator for early diagnosis of asthma, especially in predicting the risk of asthma in atopic children.