Recent findings suggest that CD14 may play a role in tumor development. Previous case-control studies have revealed that CD14 -260C/T and -651 C/T polymorphisms contribute to the risk of human diseases. However, the relationship between these two functional polymorphisms and susceptibility to acute lymphoblastic leukemia (ALL) has not been explored. In this study, we performed a case-control study in a Chinese population. We found that an increased risk of ALL was associated with the -260 TT (odds ratio [OR]=1.85, 95% confidence interval [CI]=1.26-2.63) genotype compared with the CT or CC genotype. No significant association was found between -651 CC genotype and ALL (OR=1.13, 95% CI=0.77-1.69). Moreover, the increased risk was only associated with the -260 TT genotype in B-ALL (OR=1.99, 95% CI=1.34-3.01) but not in T-ALL (OR=1.48, 95% CI=0.79-2.84). The findings suggest that CD14-260C/T polymorphism can contribute to B-ALL risk in a Chinese population.