We investigated whether molecular subtype can predict the response and prognosis in Chinese locally advanced breast cancer (LABC) patients treated with preoperative therapy. LABC patients treated with preoperative therapy in Cancer Hospital, Fudan University between August 2001 and May 2008 were retrospectively analyzed. Molecular subtypes were constructed from the immunohistochemical results of hormonal receptors (HR) and HER2 status, which were classified as luminal (HR+/HER2-), triple negative (HR-/HER2-) and HER2 positive subtypes. Preoperative tumor parameters, chemotherapy regimens and response as well as outcome were compared among these subtypes. A total of 225 cases were included into analysis. Univariate and multivariate analysis showed that the pathological complete remission (pCR) independent predictive factors were molecular subtype and preoperative regimens. Compared with luminal subtype, patients with HER2 positive or triple negative tumor had significantly higher pCR rate, with odds ratio 3.02 (95% CI=1.07-8.07; P=0.037) and 3.10 (95% CI=1.01-9.52; P=0.048), respectively. However, HER2 positive or triple negative breast cancer patients were also associated with increased recurrence (P=0.072) and death rates (P=0.019) compared with luminal subtype in the whole population, and was especially worse in patients with residual disease after preoperative therapy with decreased disease-free survival (P=0.022) and overall survival (P=0.007). Our results show that molecular subtype can predict the response and prognosis of Chinese LABC patients treated with preoperative therapy. Compared with luminal subtype, patients with HER2 positive or triple negative disease had increased pCR rates, but associated with significantly worse survival, especially in those with residual disease after preoperative therapy.