Objective To investigate the correlation between the gene expressive quantity of orosomucoid 1-like 3 (ORMDL3) and wheezing of children under 5 years old. Methods A total of 89 children with wheezing who were under 5 years old and treated at the Department of Pediatric of Renji Hospital South Campus affiliated to Shanghai Jiao Tong University School of Medicine from August 2013 to December 2014 were enrolled. According to the strict criteria of asthma predictive index (API), children were divided into API+ group (n=42) (the number of onsets of asthma ≥4 in the past year) and API- group (n=47) (the number of onsets of asthma between 1 and 3 in the past year). Health children aged less than 5 years old were selected as controls (API0 group, n=51). The gene expressive quantity of ORMDL3 of three groups was detected. The correlations of the expression level of serum ORMDL3 and API, wheezing, rhinitis, total IgE, family history, eczema, age, inhalation allergens such as dust mite, and intake allergens such as milk were analyzed. Results The expression level of serum ORMDL3 of API+ group was significantly higher than that of API- group and API0 group. The expression level of ORMDL3 was positively correlated with API (r=0.405, P=0.000), wheezing (r=0.492，P=0.000), eczema (r=0.454, P=0.000), house dust mite (r=0.298, P=0.000), dog hair and scurf (r=0.251, P=0.000), and total IgE (r=0.170, P=0.002). The expression level of ORMDL3 was not correlated with sex, family history, rhinitis, age, dermatophagoides, cat hair and scurf, tree, penicillium notatum, Piptocephalis, aspergillus fumigatus, alternaria, and dietary factors (milk, egg white, beef, cashew nut, crab, shrimp) (P>0.05). Conclusion The gene expressive quantity of ORMDL3 positively correlates with API of children, which suggests that combination of the gene expressive quantity of ORMDL3 and API can be regarded as one of evidences for the diagnosis of asthma for children under 5 years old.