Cdc27, as a core component of anaphase-promoting complex (APC), is a cell cycle regulator, which participates in control of mitotic checkpoint and surveys the mitotic spindle to maintain chromosomal integrity. It was hypothesized that polymorphisms in cdc27 gene might contribute to the susceptibility of breast cancer (BC) through influencing the mitotic progression of cells. Therefore, a hospital-based case-control study with 463 BC patients and 536 controls was implemented to investigate the association of six single-nucleotide polymorphisms (SNPs) in cdc27 and BC risk in a Chinese Han population. Among the six SNPs, two SNPs of rs11570443 and rs12601027 were positively correlated with BC risk. Individuals carrying rs11570443-CT or CC genotypes showed a higher BC risk with the OR of 1.75 (95 % confidence interval (CI) = 1.13-1.69), compared with those carrying rs11570443-TT genotype. For rs12601027, an increased BC risk was significantly associated with homozygote TT genotype (odds ratio (OR) = 1.49, 95 % CI = 1.12-1.98) compared with homozygote CC and heterozygote CT genotypes. In addition, a significant interaction effect of these two SNPs was found. The rs12601027-TT in combination with rs11570443-CT/CC genotypes showed a strongly elevated risk of BC compared with rs12601027-CC/CT and rs11570443-TT genotype (OR = 1.95, 95 % CI = 1.06-3.59). These findings suggested that polymorphisms in cdc27 may contribute to the susceptibility of BC though functional studies are needed to further elucidate the underling mechanisms of the associations.