Mounting studies have associated asthma with environmental and climatic factors, but their interaction during pregnancy on childhood asthma are unclear. This study aims to investigate the interaction of in utero air pollution and environmental temperature exposure on childhood asthma, to identify key timing windows for exposure. A retrospective cohort study with 2,598 pre-schoolers was conducted during 2011-2012 in Changsha, China. Maternal exposure to three critical ambient air pollutants (PM10, SO2 and NO2, as proxies of industrial and vehicular air pollution) and temperature (T), was assessed for the 40 gestational weeks, three trimesters of gestation, and entire pregnancy by an inverse distance weighted (IDW) method. Logistic regression analysis was used to examine the association of childhood asthma with air pollution and temperature exposure. Our results showed that pre-schooler's asthma was significantly associated with SO2 and NO2 exposure in utero, ORs = 1.46 (95% CI: 1.12-1.89) and 1.67 (95% CI: 1.24-2.26) by inter quartile range (IQR) increase of their exposure respectively. Significant risk was observed for exposure of SO2 and NO2 particularly during the 1st and 2nd trimesters and their specific gestational weeks. Pre-schooler's asthma was related with high temperature expo-sure during 1st trimester, OR = 2.33 (95% CI: 1.11-4.90) by IQR increase of T exposure. Low T and high T respectively increased the asthma risk of NO2 exposure in the 1st and 3rd trimester. Boys were more susceptible to the temperature-pollution interaction on asthma development. Our study indicates that low and high tem-perature respectively during early and late pregnancy significantly increased the impact of air pollution exposure in utero on pre-schooler's asthma.