Abstract: Objective To explore the association of mitogen-activated protein kinase kinase-4 (MAP2K4) with the pathological features, prognosis and expression of estrogen receptor (ER) in patients with breast cancer. Methods The expression of MAP2K4 was detected immunohistochemically in 102 breast cancer tissues. Chi square test was used to analyze the correlation of MAP2K4 expression with the clinicopathological features of the patients. Kaplan-Meier and log rank test were used for survival analysis of the patients. Multivariate survival analysis was performed using Cox proportional hazard regression model. The correlation between the expressionsof MAP2K4 and ER was investigated using Spearman rank correlation test. Results Immunohistochemical analysis revealed low MAP2K4 expression in 55.9%(57/102) and high MAP2K4 expression in 44.1%(45/102) of the breast cancer tissues. The expression of MAP2K4 was significantly correlated with the pathological grades of breast cancer (P=0.011). Kaplan-Meier survival analysis showed that patients with a high expression of MAP2K4 had a shorter overall survival rate than those with low MAP2K4 expressions (P=0.009). Multivariate analysis identified high expression of MAP2K4 as the independent predictor of a poor outcome of patients with breast cancer. The expressions of MAP2K4 and ER were not significantly correlated, but ER-negative patients with a high MAP2K4 expressionshowed the shortest overall survival time. Conclusion Overexpression of MAP2K4 promotes the progression in breast cancer and is associated with a poor outcome of the patients. TheER-negativepatients with a high MAP2K4 expression have the shortest overall survival time, suggestingthe value of combined examination of MAP2K4 and ER in accurate estimation of the prognosis of breast cancer patients.