The preoperative systemic immune-inflammation index (SII) is correlated with prognosis in several malignancies. The aim of this study was to investigate the prognosis value of SII in patients with resected breast cancer.A total of 784 breast cancer patients who underwent surgical resection were consecutively investigated. The optimal cutoff value of SII was evaluated using the receiver operating characteristic (ROC) curve. The collection of SII with clinicopathological characteristic and prognosis was further evaluated.The optimal cutoff value for SII in the prediction of survival was 514 according to ROC curve analysis. A high SII was significantly correlated with younger age (P = 0.037), PR status (P < 0.001), and HER2 status (P = 0.035). Univariate analysis revealed that SII (P < 0.001), T-stage (P < 0.001), lymph node involvement post-surgery (P = 0.024), and histological grade (P < 0.001) were significantly related to DFS, and SII (P < 0.001), T-stage (P = 0.003), lymph node involvement post-surgery (P = 0.006), and histological grade (P < 0.001) were significantly associated with OS. In multivariate analysis, a high SII was an independent worse prognostic factor for DFS (HR, 4.530; 95% CI, 3.279-6.258; P < 0.001) and OS (HR, 3.825; 95% CI, 2.594-5.640; P < 0.001) in all the enrolled patients. Furthermore, subgroup analysis of molecular subtype revealed that SII was significantly associated with prognosis in all subtypes.Preoperative SII is a simple and useful prognostic factor for predicting long-term outcomes for breast cancer patients undergoing surgery.Copyright © 2021 Li, Ma, Deng, Chen, Liu, Chen and Wu.