The aim of the present study was to examine the expression of hepatocyte growth factor (HGF) in breast cancer and its effect on prognosis and sensitivity to chemotherapy. Immunohistochemistry was conducted to determine the expression of HGF in 125 breast cancer patients. The correlation between the expression level of HGF and the effect of preoperative chemotherapy or 5‑year survival rate was then investigated. The human breast cancer cell line, MCF‑7, was transfected with a HGF‑small interfering (si)RNA interference sequence. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to confirm the interference efficiency of HGF‑siRNA. An MTT assay was used to detect the proliferative activity of MCF‑7 cells following silencing of HGF and during co‑culture with epirubicin (EPI) at different concentrations. HGF was highly expressed in breast cancer patients and was not associated with patient age, location, size or hormone receptor status of the tumor (P>0.05), however, HGF expression was associated with tumor‑node‑metastasis (TNM) clinical stage, histological grade, lymph node metastasis and prognosis (P<0.05). The efficiency of chemotherapy in HGF negative patients (90%) was significantly higher (P<0.05) compared with HGF positive patients (68.75%). Following successful downregulation of HGF by HGF‑siRNA, the tolerance to EPI decreased in MCF‑7 cells. In conclusion, HGF was highly expressed in breast cancer cells and was closely associated with lymph node metastasis, prognosis and sensitivity to chemotherapy. Therefore, HGF may be a potential indicator of the prognosis and effectiveness of chemotherapy for breast cancer.