Childhood acute leukemia (AL) is the most common malignant tumor in children, but its etiology remains largely unknown. We investigated the relationship between household exposure to pesticides and childhood AL. Between 2009 and 2010 in Shanghai, a total of 248 newly diagnosed cases of AL and 111 gender-, age-, and hospital-matched controls were included. Five nonspecific dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OPPs) [including dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP)] in the urine were analyzed by gas chromatography. The results showed that the median DMP, DEP, DMTP, DETP, and DEDEP levels adjusted for creatinine (Cr) in cases (13.2, 10.0, 31.3, 8.5, and 6.1 μg g(-1), respectively) were all significantly elevated compared with those in controls (3.6, 3.6, 13.3, 2.7, and 1.7 μg g(-1), respectively) (P < 0.05). The household use of mosquito repellent was significantly associated with an increased risk of childhood AL (odds ratio (OR) = 1.9; 95% confidence interval (CI) 1.2-3.1). Moreover, higher exposures were significantly associated with an elevated risk of childhood AL for DMs, DEs, and DAPs. Our findings support the notion that the household use of pesticides may play a role in the etiology of childhood AL and provide some evidence to warrant further investigation of the link between household pesticide exposures and childhood AL in Shanghai.