PURPOSE: The current investigation examines the potential clinical value and prognostic significance of a systemic immune-inflammation index (SII) in patients with breast cancer. PATIENTS AND METHODS: A total of 477 individuals underwent neoadjuvant chemotherapy, and 308 individuals did not at our center between January 1998 and December 2016 were selected. An optimized SII threshold was generated using a receiver operating characteristic curve (ROC). The relationship between various factors and breast cancer in predicting disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: The SII < 560 group (Low SII group) and SII ≥ 560 group (High SII group) are divided according to the threshold value. SII was an independent predictor for breast cancer DFS and OS based on univariate and multivariate analyses. Low SII patients had higher mean DFS and OS in contrast to those in the high SII groups (46.65 vs 27.37 months and 69.92 vs 49.53 months). Those in the low SII cohort who also had early or advanced breast cancer, different molecular subtypes, and with or without lymph vessel invasion all had higher mean survival time of DFS and OS in contrast to those with raised SII values (P<0.05). The mean DFS and OS durations also varied based on different Miller and Payne grades (MPG) (P <0.005), and different response groups (P<0.05). CONCLUSION: SII can be used as an easily accessible and minimally invasive potential prognostic factor in individuals with breast cancer and may also guide clinicians in treating and prognosticating patients with breast cancer.