BACKGROUND Lower extremity deep vein thrombosis (LEDVT), a common postoperative breast cancer complication, depends on multiple factors, such as systemic inflammation and immune status. We assessed the preoperative systemic immune-inflammatory index (SII) as a LEDVT risk predictor and did stratified nursing intervention based on it. MATERIAL AND METHODS A retrospective analysis was conducted on 552 patients who underwent breast cancer surgery from January 2019 to May 2020. Univariate and multivariate methods were used to screen independent risk factors for postoperative LEDVT, and effects of risk stratification and nursing intervention on the validation cohort were observed. RESULTS A total of 46 patients (8.3%) developed postoperative LEDVT. Compared with the control group, the LEDVT group had older age, higher proportion of menopause, higher preoperative Autar score, SII, and plasma D-dimer level, lower albumin level, and later postoperative pathological stage, with statistically significant differences (P<0.05). Multivariate logistic regression showed SII, plasma D-dimer, and menopause were independent predictors of postoperative LEDVT. ROC curve analysis showed SII had the strongest predictive ability, with an AUC of 0.714. Subsequently, 126 patients in the validation set were stratified according to the preoperative SII score, and intensified nursing intervention was implemented for high-risk patients, resulting in a significant reduction in the incidence of LEDVT (3.3% vs 8.3%, P=0.046). CONCLUSIONS Preoperative SII level can be used as an independent risk predictor of postoperative LEDVT in breast cancer patients. Applying it for risk stratification and implementing intensified nursing intervention for high-risk patients can significantly reduce the incidence of postoperative LEDVT.