We determined the prognostic value of the systemic inflammation response index (SIRI) in patients with cholangiocarcinoma after surgery and constructed a survival prediction model based on SIRI.We recruited 328 patients with histopathologically confirmed cholangiocarcinoma from 2003 to 2017 and performed Kaplan-Meier survival and Cox analyses to analyze the prognostic value of the SIRI and identify other significant factors. A nomogram involving SIRI and other clinicopathological factors was established based on the training cohort. The concordance index (C-index), decision curve analysis, calibration plots, and Hosmer-Lemeshow test were used to evaluate the clinical utility of the nomogram and to compare it with the traditional TNM staging system. The results were validated using a separate validation cohort.The patients were randomly divided into the training (n = 232) and validation (n = 96) cohorts. In the training cohort, the independent factors derived from the Cox multivariate analysis were SIRI, platelet-to-lymphocyte ratio, jaundice, γ-glutamyl transpeptidase level, maximal tumor size, N stage, M stage, and radical surgery. Time-dependent receiver operating characteristic (ROC) curves showed higher AUC for SIRI than those for other inflammation-based biomarkers. A nomogram containing all the independent factors showed good discrimination and calibration. The C-index values for overall survival, 0.737 (95% Cl: 0.683-0.791) and 0.738 (95% Cl: 0.679-0.797) in the training and validation cohorts, respectively, were significantly better than those for the TNM staging system [0.576 (95% Cl: 0.515-0.637) and 0.523 (95% Cl: 0.465-0.581), respectively].SIRI was an independent prognostic factor for cholangiocarcinoma. A prognostic model based on SIRI might help clinicians to stratify patients more precisely and provide individualized treatment.