Background: Recent studies suggested an important relationship between tumor stress-induced phosphoprotein 1 (STIP1) and cancer. However, the expression of STIP1 in breast cancer tissues and its relationship with clinical characteristics and survival have not been investigated in humans. The aim of our work was to evaluate the association of STIP1 and the prognosis of breast cancer patients. Methods: The induded patients were followed-up by telephone and through a review of their outpatient records. The expression of STIP1 was assessed by immunohistochemistry (IHC). The 5-year recurrence-free survival (RFS) rate and the 5-year overall survival (OS) rate were the prognostic indicators evaluated by the Kaplan-Meier method. Univariate and multivariate analyses employing a Cox regression model were used to calculate hazard ratios (HRs). Results: The rate of high expression of STIP1 was 55.3% (126/228) in breast cancer tissues and 14.9% (34/228) in adjacent normal tissues (chi(2)=81.495, P<0.001). High expression of STIP1 was associated with tumor size, stage and human epidermal growth factor receptor 2 (HER-2) status. The 5-year RFS rate was 75.4% in the STIP1 high expression group and 87.3% in the STIP low expression group (chi(2) =5.721, P=0.017). The 5-year OS rate was 84.1% in the STIP1 high expression group and 94.1% in the STIP1 low expression group (chi(2) =5.814, P=0.016). STIP1 was found to be an independent relapse predictor for the adjusted HR is 1.983 (95% CI, 1.031-3.815). Conclusions: High expression of STIP1 is associated with the raw prognosis of breast cancer patients and HER-2 positive expression. STIP1 may therefore serve as a prognostic biomarker for breast cancer patients.