Hypoxia-inducible factor 1-alpha (HIF-1a) has been shown to contribute to resistance to chemotherapy in breast cancer. The purpose of this study was to investigate whether HIF-1a is predictive for pathological response and the prognostic value of HIF-1a in local advanced breast undergoing neoadjuvant chemotherapy.Two hundred twenty patients with none-metastatic locally advanced invasive breast cancer (stages II-III) that subsequently received neoadjuvant chemotherapy were included in an observational study to assess the HIF-1a protein expression by immunohistochemistry. Associations between HIF-1a expression and pathological complete response (pCR) were analyzed using univariate and multivariate analysis. Independent prognostic factors for RFS were identified by multivariate Cox's proportional hazard analysis. A P value < .05 was considered to be statistically significant.The median age was 46 years, Luminal A, Luminal B, HER2-positive, and triple-negative accounted for 3.6%, 57.7%, 7.0% and 16.0%, respectively. A total of 41 patients (18.6%) achieved a pCR after neoadjuvant chemotherapy in the present study. HIF-1α negative patients had a significantly higher pCR rate than HIF-1α positive patients (P = .027). Multivariate analysis demonstrated that HIF-1α negative expression is an independent favorable predictor of pCR. Multivariate Cox regression analysis demonstrated that the HIF-1a expression before NCT showed an independent prognostic value for RFS (HR = 4.168, 95% CI: 1.012-17.170, P = .048).HIF-1a expression correlates with pCR in breast cancer undergoing neoadjuvant chemotherapy. Absent expression of HIF-1a was associated with a better pathological response and could indicate a favorable prognosis in non-pCR breast cancer patients.