OBJECTIVE: To discuss the association between ABCB1 gene polymorphisms and adriamycin and cyclophosphamide (AC) combined with chemotherapy-induced severe neutropenia in patients with breast cancer. METHODS: 218 breast cancer patients receiving AC combined with chemotherapy were selected from our hospital during 2012-2015; PCR-RFLP was used to detect polymorphisms of ABCB1 2677G>T/A and 3435C>T. The associated between different age, BMI, clinical stages genotypes, etc and AC combined with chemotherapy-induced severe neutropenia were investigated, and risk factors of neutropenia were analyzed by multivariate logistic regression. RESULTS: Among 218 breast cancer patients, 170 patients suffered from severe neutropenia, accounting for 78.0%. Among ABCB1 2677G>T/A polymorphisms, distribution frequency of GT or GA genotype, TT, TA or AA genotype, GG genotype in severe neutropenia were 80.6%, 86.2% and 60.0%, with statistical significance (P<0.05). Among ABCB1 3435C>T polymorphisms, distribution frequency of TT, CT and CC genotype in severe neutropenia were 86.4%, 78.4% and 72.7%, there was no statistical significance (P>0.05). AST and ABCB1 2677G>T/A polymorphisms were correlated with severe neutropenia (P<0.05), and ABCB1 2677G>T/A polymorphism was a strong predictor of neutropenia [OR=3.875,95%CI(1.555,9.922),P=0.008]. CONCLUSIONS: ABCB1 2677>T/A polymorphisms may be aggravate AC combined with chemotherapy-induced neutropenia in patients with breast cancer.