Abstract: To assess the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) in gastric carcinoma and to determine the correlation with the clinicopathologic features and chemosensitivity of 5- fluorouracil (5- FU). Methods: ELISA was used to detect expression of the TP and DPD proteins in tumor tissue and adjacent normal tissue of 52 patients with gastric carcinoma. The relationship between the TP and DPD protein levels and clinicopathological features of gastric cancer was analyzed. MTT assay was employed to evaluate the 5- FU sensitivity of gastric cancer cells in vitro and this data was used to investigate the correlation between TP and DP levels and sensitivity to 5-FU. Results: In gastric cancer, both TP and DPD protein levels were significantly higher compared to the normal paraneoplastic tissues (TP: 65.82±31.90 vs. 17.47±12.26 U/ mg protein, P<0.001; DPD: 24.48±10.87 vs. 11.89±4.35 U/mg protein, P<0.001). The expression of TP protein showed a positive correlation with lymph node metastasis (P=0.028), TNM staging (P=0.019) and pathologic differentiation (P=0.033), whereas the DPD protein tended to be highly expressed only in intestinal gastric cancer (P=0.001) compared to the asystematic type. DPD expression was inversely associated with 5- FU sensitivity (rs=0.426, P=0.019), but no significant correlation was found between TP expression and 5- FU sensitivity (rs=0.179, P=0.344). Conclusion: TP and DPD protein expression in tumor tissues is significantly higher than levels found in normal paraneoplastic tissues. There is a close correlation between TP expression and clinical staging of gastric cancer, and between DPD expression and Laurén grouping with the intestinal- type gastric cancer. A low level of DPD expression may be used as a predictor for 5- FU chemosensitivity.