Objective To explore the predictive value of preoperative inflammatory indicators combined with tumor biomarkers for lymph node metastasis of intrahepatic cholangiocarcinoma (ICC). Methods A total of 105 patients who underwent radical resection and lymph node dissection for ICC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi’an Jiaotong University from January 2010 to December 2020 were retrospectively analyzed. Among them, 49(43.8%) patients were male and 56 (56.2%) patients were female, aged from 29 to 81 years with an average of (57.85±10.29) years old. ROC curve was conducted to determine the best cut-off values of each preoperative inflammatory indicator. The 2 test was conducted for comparison between groups, the Kaplan-Meier method and Log-rank test were conducted for univariate analysis. Results All 105 patients included in this study, there were 62 patients N0 stage and 43 patients with N1 stage. The median survival time of N0 stage and N1 stage patients was 32 months and 9.0 months, respectively; the overall survival rates of 1 and 3 years were 79.2%, 41.2% and 36.4%, 12.0% for patients with N0 and N1 stages, respectively. By evaluating the predictive value of different preoperative inflammatory indicators and tumor biomarkers for lymph node metastasis of ICC, the results that the systemic immune-inflammation index (SII) and the CA19-9 had best predictive ability on lymph node metastasis (area under the ROC curves: 0.662, 0.707, 95% CI:0.553~0.770, 0.606~0.808, P＜0.05). In N1 stage patients, the ratio of SII＞752.87 and CA19-9＞39.0U/mL was significantly higher than that of N0 patients (2=6.641, 6.244, P＜0.05). Survival analysis showed that SII and CA19-9 were the risk factors affecting the prognosis for ICC (HR=1.881, 2.176, 95%CI: 1.133~3.123, 1.293~3.663, P＜0.05). The combination of inflammation indicators and tumor biomarkers was used to predict lymph node metastasis, and the results showed that the combination of SII+CA19-9 had the best predictive ability for lymph node metastasis, and the area under the ROC curve was 0.782 (95%CI: 0.692~0.872, P＜0.001). After further grouping the combined SII+CA19-9, the survival difference of patients in each group was statistically significant (P=0.001).Conclusion The preoperative inflammatory indicator SII combined with CA19-9 has good diagnostic value for lymph node metastasis of intrahepatic cholangiocarcinoma, and has a good ability to evaluate postoperative prognosis.