Background: The clinical behaviors of de novo metastatic breast cancer (dnMBC) differ according to hormone receptor (HR) status, but an association between estrogen receptor (ER) expression and clinical outcomes has not been established. Our study aimed to investigate the influence of different ER status on survival outcomes for patients with dnMBC. This study was the Medical Science Research Project of Hebei Province and approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO. 2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types and survival data. According to ER status, the patients were divided into ER-negative and ER-positive groups, and the propensity score matching (PSM) was used to balance the mixed bias. Overall survival (OS) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results: A total of 322 patients were included. The median age was 53 (21-82) years, and the median follow-up was 8.5 years. The median OS for the PSM cohort was 29 months (95% confidence interval [CI], 26-35 months), and 5-year OS was 18.9%. OS differed significantly between the two groups (p = 0.0012), with a median OS of 36 months (95% CI, 32-41 months) in ER-positive group and 24 months (95% CI, 19-27 months) in ER-negative group. Multivariate analysis showed that clinical T-stage and initial metastatic sites were independent prognostic factors for survival in patients focused on ER status, with Ki-67 index, endocrine therapy and radiotherapy added to the ER-positive group, while initial and advanced chemotherapy added to the ER-negative group. Conclusions: For patients with dnMBC, there were substantial differences in OS according to ER status. ER-negative subtype is clinically different from ER-positive subtype, showing unfavorable tumor characteristics and poorer OS. We identified several prognostic factors that could guide therapy selection in this patient population. Clinical trial information: 20210957.