Abstract: Objective Breast cancer remains a major cause of death in women worldwide,and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment.This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response:myeloid differentiation primary response 88(MyD88) and Toll-like receptor 4(TLR4). Methods We analyzed data of 200 breast invasive ductal carcinoma(IDC) patients who were treated at the department of breast surgery,the First Affiliated Hospital of Xinjiang Medical University from 2005 to 2007.Overall survival(OS) and disease free survival(DFS) were compared. Results In total,153 patients(76.50%) were disease-free without relapse or metastasis,whereas 47(23.50%) patients developed recurrence or metastasis.A significant positive correlation was observed between MyD88 and TLR4 expression(P<0.001).Patients with high expression were more likely to experience death and recurrence/metastasis events(P<0.05).Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels(log-rank test,P<0.001).Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test,P<0.001).In a multivariate analysis,high MyD88 expression was an independent predictive factor for decreased DFS(adjusted HR,3.322;95% CI:1.663-6.631;P=0.001) and OS (adjusted HR,4.500;95% CI:1.544-13.098;P=0.005). Conclusion TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer.Therefore,TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.