Objective To explore the expression and clinical significance of aldo-keto reductase 1-A1 (AKR1A1) in hilar cholangiocarcinoma tissues. Methods Immunohistochemical assay was used to detect the expression of AKR1A1 in 49 hilar cholangiocarcinoma and adjacent normal tissues (at least 2 cm from the edge of the tumor). The correlation between the AKR1A1 expression and clinical variables of hilar cholangiocarcinoma patients was analyzed by χ² test. Results The high-expression rate of AKR1A1 in cancer tissues was 59.2% (29/49), which was significantly higher than that in matched adjacent normal tissues (25.0%[3/12], P<0.05). We also noticed that the high-expression of AKR1A1 in hilar cholangiocarcinoma patients tissues was associated with tumor size (P=0.028) and lymph node metastasis (P=0.001). Survival analysis showed that the overall survival (median 15 months vs 39 months, P=0.012) and progression free survival (median 15 months vs 32 months, P=0.022) of AKR1A1-high-expression patients were significantly shorter compared with the low-expression patients. Multivariate analysis showed that the depth of invasion was associated with overall survival (odds ratio[OR] 0.174, 95% confidence interval[CI] 0.041-0.741, P=0.018) and progression free survival (OR 0.083, 95% CI 0.011-0.618, P=0.015). Conclusion AKR1A1 is involved in the progression and metastasis of hilar cholangiocarcinoma, suggesting that it might be a potential biomarker for predicting tumor recurrence and prognosis of patients with hilar cholangiocarcinoma.