BACKGROUND: 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. METHODS: 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. RESULTS: 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) CONCLUSIONS: Our study demonstrates that elevated SII is an independent adverse prognostic factor for LS-SCLC.