Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. Surgery is the main way to cure CRC, but the postoperative complication rate and recurrence rate remain high. The systemic immune-inflammation (SII) index reflects a patient's systemic inflammatory state and immune state. Postoperative recurrence and the occurrence of complications are closely related to the inflammatory state and immune state. Thus, the SII index may have some value in predicting postoperative complications and the long-term prognosis of CRC patients, but relevant studies are currently lacking. The present study sought to examine the effect of the SII index on the postoperative complications and long-term prognosis of patients with CRC.From January 2014 to January 2017, the data of 440 patients with CRC who had been admitted to the Affiliated Hospital of Guangdong Medical University were retrospectively collected, and the patients were equally divided into the high and the low SII groups according to their preoperative SII index levels. The postoperative complication rate and postoperative progression-free survival (PFS) and mortality between the 2 groups were compared.Compared to the low SII group, the incidence of postoperative infection in the high SII group was significantly increased (15.45% vs. 9.09%, P=0.042), mortality was significantly increased at 5 years postoperatively (20.91% vs. 7.27%, P<0.001), and PFS was significantly shortened (P<0.001). The SII index had certain predictive value for postoperative infection in CRC patients, and the area under the curve (AUC) was 0.645 [95% confidence interval (CI): 0.559-0.731, P=0.001]. The SII index also had certain predictive value for the progression of CRC patients within 5 years of surgery, and the AUC was 0.670 (95% CI: 0.610-0.729, P<0.001). Additionally, the SII index had certain predictive value for death within 5 years of surgery in patients with CRC, and the AUC was 0.660 (95% CI: 0.593-0.726, P<0.001). CRC patients with postoperative infection had a significantly shorter PFS period than those who did not develop postoperative infection (P=0.029).The SII index has certain predictive value for the diagnosis of postoperative infectious complications and the long-term prognosis of CRC patients.2022 Journal of Gastrointestinal Oncology. All rights reserved.