Abstract: Objective To investigate the association between paternal-related factors and the susceptibility of childhood acute leukemia (AL). Methods Based on case-control study, AL children and their 1:1 controls matched with residential region, age and gender were recruited from four hospitals in Henan Province from 2014 to 2016. Propensity score matching (PSM) was used to equalize covariates, the matching effect was verified by standardized difference method. Conditional Logistic regression was used to analyze the association between variables and childhood AL with the matched data.The adjusted population attributable risk percent (PARP)and subgroup analyses were performed. Results A total of 407 cases and 407 controls were included in the analysis. A total 270 pairs of cases and controls were matched by PSM. The standardized difference values of 16 covariates were less than 0.1 after PSM. Conditional Logistic regression showed that paternal exposure to pesticides (OR_adj=1.93, 95% CI:1.23-3.05), hair coloring (OR_adj=2.31, 95% CI:1.04-5.12) 6 months before pregnancy increased the risk of childhood AL, of which PARP were 11.42%, 4.62% respectively. The relationship between paternal exposure to pesticides and childhood AL were still obvious in sub-population with male, age at diagnosis less than 5 years old, rural residents, and those with paternal exposure to tobacco (all P<0.05). Conclusion Paternal exposure to pesticides, hair coloring 6 months before pregnancy can increase the susceptibility of childhood AL, which should be controlled in prenatal care.