Excision repair cross-complementation group 1 (ERCC1) is important in repairing DNA damage and genomic instability, and polymorphisms in ERCC1 may play a role in human tumors. In this study, the relationship of two ERCC1 polymorphisms, 8092C>A and 19007G>A, with susceptibility to acute lymphoblastic leukemia (ALL) was investigated in 183 childhood patients. For the ERCC1 8092C>A polymorphism, individuals carrying the ERCC1 8092CC genotype had a significantly higher risk when compared with those carrying at least one A allele gene (AA/AC). Analysis after stratification for sex showed that the males carrying ERCC1 8092CC genotype were associated with highly significant increased risk of ALL (1.94-fold) but not females. There was no association between ERCC1 19007G>A polymorphism and ALL risk when all patients as a group were analyzed. However, the males carrying ERCC119007A allele were associated with highly significant increased risk of ALL (2.36-fold). For the ERCC1 8092C>A polymorphism, individuals under 8 years old (median age) carrying CC genotype had significantly higher risk. However, the 19007G>A polymorphism was not associated with such age-related ALL risk. These results suggest that the ERCC1 8092C>A polymorphism may be related to the occurrence of childhood ALL in a Chinese population.