Objective To investigate the prognosis of patients with hepatitis B virus (HBV)‑related intrahepatic cholangiocarcinoma (ICC) whose HBV DNA was negative before surgical. Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017. All patients were divided into HBV-related ICC (HBV-ICC) group (n=62) and non-HBV-related ICC (Con-ICC) group (n=35). HBV-ICC group included 34 patients with HBV core antigen positive (HBcAb⁺) and HBV surface antigen positive (HBsAg⁺), and 28 patients with HBcAb positive and HBsAg negative. Kaplan-Meier analysis was used to plot survival curves and compare the overall survival (OS) and postoperative recurrence-free survival (RFS) among patients in Con-ICC, ICC patients with HBsAg⁺/HBcAb⁺, and ICC patients with HBsAg^-/HBcAb⁺. Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS, RFS and early postoperative recurrence among gender, age, pathogenic factor, liver cirrhosis, Child-Pugh grade, carbohydrate antigen 19-9 (CA199), alpha-fetoprotein (AFP), glutamine transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), American Joint Committee on Cancer (AJCC) stage, tumor size, tumor number, tumor differentiation, microvascular invasion, lymph node metastasis, hepatectomy procedure, cholecystectomy, and follow-up treatment. Results Of the 97 patients, the median age was 56 years, and 79 (81.4%) of them were male. The median follow-up time was 92.2 months. Eighty-eight (90.7%) patients presented with tumor recurrence and 73 (75.3%) died. In multivariate analyses, HBV-ICC and CA199>37 kU/L were independent predictors of OS (HR=0.45, 95%CI 0.26-0.77, P=0.003; HR=2.10, 95%CI 1.24-3.57, P=0.006), RFS (HR=0.43, 95%CI 0.27-0.68, P<0.001; HR=1.78, 95%CI 1.12-2.81, P=0.014), and postoperative early recurrence (HR=0.42, 95%CI 0.26-0.70, P=0.001; HR=2.02, 95%CI 1.20-3.39, P=0.008). AJCC stage Ⅲ was an independent risk factor for postoperative RFS (HR=1.81, 95%CI 1.04-3.14, P=0.037). Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence (HR=1.73, 95%CI 1.07-2.77, P=0.024; HR=1.90, 95%CI 1.12-3.24, P=0.017). There was no statistically significant difference in OS, RFS, and early recurrence between HBV-ICC patients with HBsAg^-/HBcAb⁺ and Con-ICC patients (P<0.05), whereas HBsAg⁺/HBcAb⁺ was a significant factor affecting postoperative OS (HR=0.32, 95%CI 0.16-0.62, P=0.001), RFS (HR=0.32, 95%CI 0.18-0.55, P<0.001), and early recurrence (HR=0.29, 95%CI 0.15-0.54, P<0.001) in ICC patients. Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA^- is better than that of Con-ICC patients. The prognosis of HBV-ICC patients with HBcAb⁺/HBsAg^- is worse than that of HBV-ICC patients with HBcAb⁺/HBsAg⁺, but similar to Con-ICC patients. Therefore, the postoperative stratified management of HBV-ICC patients should be emphasized.