Objective To investigate the relationship between the eighth edition of American Joint Committee on Cancer (AJCC) staging, preoperative prognostic nutritional index (PNI) and the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) treated with different lymph node dissection methods. Methods 105 ICC patients admitted to our hospital from January 2019 to January 2021 were selected for study by combining retrospective analysis and case-control study. All patients received radical tumor resection, and 59 patients were treated with en bloc fusion dissection for lymph node dissection (group A). Another 46 patients were treated with traditional routine lymph node dissection (group B), and the two groups of patients were followed up for 1 year to observe the survival rate and survival time. Logistic regression model was used to analyze the key factors affecting the prognosis of patients. Results After 18-month follow-up, the survival rate of patients in group A was 84.75%, and that in group B was 67.39%. Group A was significantly higher than group B, and the difference was statistically significant (P＜0.05).The survival time of patients in group A was longer than that in group B, and the difference was statistically significant (Log Rank (Mantel-Cox)=4.994, P=0.025) The proportion of dead patients with T stage ≥T2 stage, N1 stage in N stage, TNM stage ≥Ⅱ stage, and PNI index ≥45.0 were significantly higher than those in the survival group, and the difference was statistically significant (P＜0.05) Logistic regression model results showed that: TBIL≥20.0 μmol/L, multiple tumors, vascular invasion, intraoperative blood transfusion, N1 stage, TNM stage≥Ⅱ, and PNI index ＜45.0 were independent risk factors for poor prognosis in patients with ICC (P＜0.05) Conclusion According to the AJCC staging and preoperative PNI level of ICC patients, the prognosis of patients after radical resection can be preliminarily evaluated. En bloc dissection of lymph nodes during radical resection is beneficial to prolong the survival time of patients