In clinical practice, breast cancers with lymph node positive, ER/PR-negative and overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high risk of recurrence, but the effective biomarkers of prognostic for this type tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins between those two groups could be related to the risk of recurrence. Herein, we report that serum soluble CD14 (sCD14) was revealed as the stable differential protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer patients by proteomics analysis. To validate sCD14 as a biomarker for predicting recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93 patients with LN-ER/PR+Her2- were recruited. The patients with higher level of serum sCD14 at primary surgery showed to be at significantly lower risk of relapse in 3 years follow-up than those with lower level of serum sCD14 at primary surgery. The levels of serum sCD14 at primary surgery were significantly correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920). Therefore, we surmise that serum sCD14 could be a potential biomarker for predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.