ErbB2 is overexpressed in 15-20% of breast cancer, which is associated with malignancy and poor prognosis. We previously reported that ErbB2 supports malignant progression of breast cancer by upregulating lactate dehydrogenase A (LDHA), an important enzyme in glycolysis. However, whether ErbB2 promotes breast cancer progression through other glycolytic enzymes remains unclear. Hexokinase 1 (HK1) and hexokinase 2 (HK2) are the first rate-limiting enzymes of glycolysis and both of them are increased in breast cancer. Here, we aim to investigate whether ErbB2 upregulates HK1 and HK2 and the role of HK1 and HK2 in the malignant progression of ErbB2-overexpressing breast cancer. In current study, we found that the mRNA level of ErbB2 was positively correlated with that of HK1 and HK2, respectively. Moreover, ErbB2 upregulated the protein levels of HK1 and HK2 in breast cancer cells. We also found that both siHK1 and siHK2 significantly inhibited the proliferation, migration and invasion of ErbB2-overexpressing breast cancer cells. Taken together, our findings suggested that ErbB2 promoted the malignant progression of breast cancer cells by upregulating HK1 and HK2, and HK1 and HK2 might serve as promising therapeutic targets for ErbB2-overexpressing breast cancer.