Abstract: Objective: To approach the dependability between polymorphism of the exon 4(870 A/G) of cyclin D1 and Acute Lymphoblastic Leukemia (ALL) in children. Methods: A case-control study consisting of 183 children ALL patients and 190 controls in a Chinese population was performed to examine the genotypic frequency of the cyclin D1 polymorphism. Results: The genetic frequency of cyclin D1 significantly correlated with overall patients and controls. AA genotype of cyclin D1 showed a tendency to increase ALL risk by 3.289 8-fold compared to AG + GG (P=0.020 7). Stratification of patients according to cell type, risk level and the chemotherapeutic response showed that the AA genotype was clearly observed in T-ALL, and the ALL with high risk (P=0.047 and P= 0.011 respectively). No gene dosage effect was observed in this study. Conclusion: The cyclin D1 genetic polymorphism might be closely related to the occurrence of children ALL in the Chinese population.