Given the role of inflammation in cancer progression, the systemic immune-inflammation index (SII, defined as platelet × neutrophil/lymphocyte) has been suggested as an emerging prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage small cell lung cancer (LS-SCLC), and the optimal threshold of SII remains unclear in this population. This study calculated the optimal threshold of SII by a reasonable method and explored its association with survival outcomes.This retrospective study reviewed clinical data of 572 patients with LS-SCLC. The threshold for SII was determined using an outcome-based method by maximizing the log-rank test statistic and the survival differences. Continuous time-dependent receiver operating characteristic curves (time-dependent ROC curves) were used to clarify the predictive ability of SII.The thresholds of SII for overall survival (OS) and progression-free survival (PFS) were both 760.6, based on which patients were divided into low [292 cases (51.0%)] and high [280 cases (49.0%)] SII groups. The area under the time-dependent ROC curves of SII in 12-, 24-, and 36-months were 0.727, 0.708, and 0.680, respectively. The overall median OS and PFS were 26.0 months [95% confidence interval (CI): 23.8-28.2] and 13.0 months (95% CI: 11.3-14.7), respectively. Significantly improved OS [35.0 (95% CI: 30.0-40.0) vs. 19.0 months (95% CI: 17.1-20.9), P<0.001] and PFS [20.0 (95% CI: 17.3-22.7) vs. 11.0 months (95% CI: 9.9-12.1), P<0.001] was seen in the low SII group than that in the high SII group. In the multivariable survival analysis, SII remained an independent prognostic factor for OS [hazard ratio (HR): 1.699; 95% CI: 1.374-2.100; P=0.001] and PFS (HR: 1.482; 95% CI: 1.214-1.809; P<0.001).Our study demonstrates that elevated SII is an independent adverse prognostic factor for LS-SCLC.Copyright © 2025 AME Publishing Company. All rights reserved.