To investigate an association between maternal prenatal exposure to several environmental factors and risk of childhood acute lymphocytic leukemia (ALL), and the possible interactions in the Chinese population. 345 cases with ALL and their 1:1 age, gender, residence region matched controls aged 0-15 years were recruited from four hospitals in Henan Province from 2014 to 2016. Information was collected by interviews using a questionnaire. Unconditional logistic regression adjusted for age, gender, residence region and relevant confounders was carried out to generate the odds ratios (ORs) and 95% confidence intervals (CIs). Our data indicate that maternal prenatal exposure to interior housing renovation (adjusted OR: 2.98, 95% CI: 1.51-5.86) or pesticides (adjusted OR: 1.48, 95% CI: 1.67-2.28) increased the risk of childhood ALL. Various subgroup analyses stratified by child's gender, age at diagnosis and other factors also supported these results. However, no interaction was detected between exposure to internal housing renovation and pesticides using an additive model. No significant links between maternal exposures to, environmental tobacco smoking (ETS), antipyretic analgesia intake, or viral infectious diseases with risk of ALL were detected. Findings in our study are in line with the existing literatures, which support the hypothesis that maternal prenatal exposure to interior housing renovation and pesticides are risk factors for childhood ALL. Notably, we found no interaction between these two risk factors, these findings may inform prevention and early detection strategies.