Objective: To investigate the correlations between the systemic immune inflammatory index (SII) and prognosis of patients with gallbladder cancer. Methods: From April 2005 to January 2019, patients with gallbladder cancer underwent surgical treatment in the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Zhengzhou University were followed up and their SII values were analyzed. The receiver operating characteristic curve (ROC) was used to determine the best clinical boundary value of SII. According to the boundary value, patients were divided into two groups: low SII and high SII. Survival curves were drawn by Kaplan-Meier method. The overall survival time of the two groups was analyzed, and univariate analysis of postoperative survival was performed using log-rank test. Cox regression proportional hazard model was used for multivariate analysis of clinical prognosis. Results: A total of 312 patients were included, including 120 males and 192 females, aged 30.0 to 86.0 (61.5±9.9) years. The best clinical cut off value of preoperative SII was determined by ROC curve to be 510.42. A total of 312 patients with gallbladder cancer were divided into low SII group (SII≤510.42) and high SII group (SII>510.42). Kaplan-Meier survival curve was used to analyze the 1, 3 and 5-year survival rates of gallbladder cancer patients in low SII group and high SII group after operation. The survival rates were 65.7%, 39.6% and 30.2%, and 27.9%, 12.0% and 9.6% respectively. The median survival time was 25 months (95% CI: 16.9-33.1) and 9 months (95% CI: 8.1-9.9), respectively. The survival rate of gallbladder cancer patients in low SII group was better. There were significant differences of the overall survival rate between the two groups (P<0.05). Univariate analysis showed that SII>510.42 (HR=0.086, 95% CI: 0.032-0.289) was a risk factor for overall survival of gallbladder cancer patients. Cox multivariate analysis confirmed that preoperative SII (HR=2.649, 95% CI: 1.981-3.543) was an independent risk factor for overall survival of gallbladder cancer patients. Conclusions SII can be used as an independent prognostic factor to predict the prognosis of patients with gallbladder cancer. The higher the preoperative SII, the worse the prognosis of patients with gallbladder cancer.