Background: The preoperative systemic inflammation response index (SIRI), based on peripheral neutrophil (N), monocyte (M), and lymphocyte (L) counts, has shown mounting evidence as an effective prognostic indicator in some malignant tumors. The aim of the present study was to evaluate the prognostic significance of pre-treatment SIRI in gastric cancer patients who received neoadjuvant chemotherapy (NACT). Methods: This retrospective study comprised 107 patients with advanced gastric cancer treated with NACT between July 2007 and September 2015 in our hospital. SIRI was calculated from peripheral venous blood samples obtained prior to treatment. The best cutoff value for SIRI by receiver operating characteristic (ROC) curve was 1.2 (low SIRI <1.21, high SIRI ≥1.21). The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model. Results: The results demonstrated that the low SIRI group was statistically associated with gender, primary tumor site, white blood cell, neutrophil, and monocyte counts, NLR (neutrophil to lymphocyte ratio), MLR (monocyte to lymphocyte ratio), and PLR (platelet to lymphocyte ratio). The SIRI was predictive for DFS and OS by univariate and multivariate analysis; the low SIRI group had better median DFS and OS than the high SIRI group (median DFS 27.03 vs. 22.33 months, median OS 29.73 vs. 24.43 months). The DFS and OS in the low SIRI group were longer than the high SIRI group. Conclusions: SIRI may qualify as a useful, reliable, and convenient prognostic indicator in patients with advanced gastric cancer to help physicians to provide personalized prognostication for gastric cancer patients treated with NACT.Copyright © 2021 Chen, Chen, Zhang, Xue, Zhang, Li and Song.