The prognostic value of SII (Systemic Immune-Inflammation Index) in HER-2-positive breast cancer (BC) patients, regardless of whether they receive trastuzumab treatment, and its potential value to distinguish patients who may benefit from trastuzumab therapy, warrant further investigation. Clinical data was collected from 797 HER-2-positive BC patients between July 2013 and March 2018. Baseline data differences were adjusted with propensity score matching. Univariate and multivariate analyses explored the correlation between clinical pathological factors, SII, and DFS. Four groups were established. Based on the baseline SII values of the participants, patients who did not receive trastuzumab treatment were divided into Group 1 (Low-SII) and Group 2 (High-SII), where SII had no predictive value for prognosis between groups. Participants who received trastuzumab treatment were also divided into two groups: the Low-SII group (Group 3) and the High-SII group (Group 4). The 5-year DFS was significantly higher in Group 3 than in Group 4 (91.76% vs. 82.76%, P = 0.017). Furthermore, multivariate analysis demonstrated a significant association between high SII and shorter DFS (HR = 3.430, 95% CI = 1.830-6.420, P < 0.001). In HER-2-positive BC patients treated with trastuzumab, those with lower SII showed a longer DFS, suggesting that SII may help in identifying patients who benefit from trastuzumab therapy.