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Objective: Although the prognosis in patients with biliary carcinoma remains poor, adjuvant gemcitabine-based chemotherapy after surgical resection for biliary carcinoma has been shown to improve survival. There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. To clarify the relationship between expression of intratumoral enzymes related to the metabolism of gemcitabine and its derivatives and response to adjuvant chemotherapy with gemcitabine for cholangiocarcinoma, we evaluated human equilibrative nucleoside transporter 1 (hENT1) expression immunohistochemically in resected cholangiocarcinoma tissues. Methods: Polyclonal antibodies were used to immunostain sections of 105 formalin-fixed paraffin-embedded specimens of cholangiocarcinoma resected between 1989 and 2010. The relationship between intratumoral hENT1 expression and prognosis was evaluated statistically. This study was a retrospective analysis on retrospectively collected tissue and data. Results: Out of 105 patients, 51 (49%) received adjuvant gemcitabine-based chemotherapy. High and low intratumoral hENT1 expression was present in 74 (70%) and 31 (30%) cases, respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival of patients with high hENT1 expression was significantly better than that of patients with low hENT1 expression among patients who received adjuvant gemcitabine-based chemotherapy (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received adjuvant gemcitabine-based chemotherapy and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with adjuvant gemcitabine-based chemotherapy by multivariate analysis (P = 0.027). Conclusion: High intratumoral hENT1 expression was associated with increased overall survival in patients with cholangiocarcinoma who received adjuvant gemcitabine-based chemotherapy. Intratumoral hENT1 expression may be a potent predictive marker for cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy.