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Background&Aim: Although intratumoral dihydropyrimidine dehydrogenase (DPD) and human equilibrative nucleoside transporter 1 (hENT1) expression has been reported to be associated with chemosensitivity to each fluoropyrimidine and gemcitabine, their impact on combined chemotherapy is unclear. The aim of this study is to investigate whether intratumoral DPD and hENT1 expression can predict survival of pancreatic carcinoma patients treated with adjuvant gemcitabine plus S-1 (GEM+S-1) chemotherapy.Methods: Intratumoral DPD and hENT1 expression was investigated by immunohistochemistry in 86 pancreatic adenocarcinoma patients who received adjuvant GEM+S-1 chemotherapy after surgical resection. Associations between clinicopathological factors including DPD and hENT1 expression and disease free survival (DFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Furthermore, we classified all 86 patients into the three groups according to the number of favorable factors related to DPD and hENT1 expression. (2 favorable factors: low DPD and high hENT1, 1 favorable factor: low DPD and hENT1 or high DPD and hENT1, 0 favorable factor: high DPD and low hENT1). Association between this combined classification and survival was also evaluated.Results: High DPD and hENT1 expressions were observed in 35 (41%) and 63 (72%) patients, respectively. According to the combined classification with DPD and hENT1, 37 (43%), 41 (48 %), and 8 (9%) patients had 2, 1, and 0 favorable factors, respectively. Univariate analysis revealed that patients with low DPD expression had significantly longer DFS (P=0.006) and OS (P=0.011) than those with high DPD, and patients with high hENT1 expression had significantly longer DFS (P=0.003) and OS (P=0.003) than those with low hENT1. The combined classification with DPD and hENT1 was also significantly associated with DFS (P<0.001) and OS (P<0.001). Sub-analysis between each two of the three groups revealed that patients with 2 favorable factors had significantly longer DFS and OS than those with 1 (DFS: P=0.017, OS: P=0.016) and than those with 0 (DFS: P<0.001, OS: P<0.001). Patients with 1 favorable factor had significantly longer DFS (P=0.004) and OS (P=0.002) than those with 0. In multivariate analysis, each DPD and hENT1expression were independently associated with DFS (DPD: P=0.003, hENT1: P=0.004) and OS (DPD: P=0.032, hENT1: P=0.026). The combined classification with DPD and hENT1 was also independently associated with DFS (P<0.001) and OS (P=0.004).Conclusion: Analysis of intratumoral DPD and hENT1 expression enables the stratification of pancreatic adenocarcinoma patients treated with adjuvant GEM+S-1 chemotherapy based on their likelihood of survival, and may have a potential to optimize adjuvant chemotherapy including gemcitabine and S-1 for resected pancreatic adenocarcinoma.