Background Explore markers to predict the clinical outcomes of checkpoint inhibitors have high unmet needs. The following study investigates whether hematologic parameter such as systemic immune‐inflammation index (SII), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) is associated with nivolumab efficacy in advanced non‐small‐cell lung cancer (NSCLC). Methods Advanced/metastatic NSCLC patients treated with nivolumab monotherapy for second‐line or further‐line treatment at Jilin Cancer Hospital between March 2016 and July 2018 were enrolled in this retrospective study. The optimal cutoff values of SII, NLR, and PLR for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve. Progression‐free survival (PFS) and overall survival (OS) were calculated and compared using Kaplan‐Meier method and log‐rank test. Prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses. Results A total of 44 patients with advanced NSCLC were included; the median age was 60 (range: 43‐74). The optimal cutoff value of SII/NLR/PLR predicted PFS and OS was 603.5, 3.07, and 144. Low SII, NLR, and PLR were associated with longer PFS (HR for SII = 0.34, 95%CI 0.15‐0.76, P = 0.006; HR for NLR = 0.46, 95%CI 0.22‐0.99, P = 0.048; HR for PLR = 0.39, 95%CI 0.17‐0.94, P = 0.025) and OS (HR for SII = 0.16, 95%CI 0.05‐0.51, P = 0.005; HR for NLR = 0.20, 95%CI 0.06‐0.62, P = 0.002; HR for PLR = 0.20, 95%CI 0.06‐0.73, P = 0.008). NLR ≤ 3.07, PLR ≤ 144, SII ≤ 603.5 were independently associated with longer PFS and OS. Conclusion The SII, NLR, and PLR are promising prognostic predictor for patients with metastatic NSCLC patients.

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