AIM To investigate the clinical significance of preoperative systemic immune-inflammation index(SII) in patients with colorectal cancer(CRC). METHODS A retrospective analysis of 1383 cases with CRC was performed following radical surgery. SII was calculated with the formula SII =(P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. The clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices such as the neutrophil-lymphocyte ratio(NLR) and platelet-lymphocyte ratio(PLR) in patients with CRC.RESULTS The optimal cut-off point for SII was defined as 340. The overall survival(OS) and disease-free survival(DFS) were better in patients with low NLR, PLR, and SII(P < 0.05). The SII was an independent predictor of OS and DFS in multivariate analysis. The area under the receiver-operating characteristics(ROC) curve for SII(0.707) was larger than those for NLR(0.602) and PLR(0.566). In contrast to NLR and PLR, SII could effectively discriminate between the TNM subgroups. CONCLUSION SII is a more powerful tool for predicting survival outcome in patients with CRC. It might assist the identification of high-risk patients among patients with the same TNM stage.