<p>Cholangiocarcinoma is a common malignant tumor that seriously endangers physical and mental health. Elevated serum ferritin levels are correlated with reduced survival and increased recurrence rates in various cancers. The present study aimed to evaluate the potential of serum ferritin as a prognostic biomarker in cholangiocarcinoma. Immunoassay was used to detect ferritin protein in the serum of 120 cholangiocarcinoma patients and to compare the diagnostic utility of the conventional tumour markers CEA, CA19-9 and CA125. The median DFS for all patients was 420 days (range, 1.0-51.8 months). Median survival was 991 days (range, 2.1–51.8 months) and 361 days (range, 1.0-51.8 months) in the low- and high-ferritin level groups, respectively (<i>P</i> &lt; 0.001). Patients with cholangiocarcinoma with low ferritin expression (≤ 196.5 ng/ml) had significantly higher disease-free survival than those with high ferritin expression (&gt; 196.5 ng/ml). The findings of multivariate analyses showed serum ferritin (<i>P</i> = 0.001), CA19-9 (<i>P</i> = 0.037), Tbil (<i>P</i> = 0.017), and Ki67 (<i>P</i> = 0.008), lymph node metastasis (<i>P</i> = 0.040) and no lymph node dissection (<i>P</i>&lt;0.001) were considered as independent factors affecting the prognosis. Ferritin levels had statistically significant relationship between patient’s CA19-9 level, Vascular invasion, CD34/31 expression and Postoperative adjuvant therapy (<i>P</i> &lt; 0.05). These results indicate that serum ferritin is prognostically associated with patients with cholangiocarcinoma and may serve as a valuable prognostic biomarker for patients with cholangiocarcinoma.</p>