It has been reported that thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and excision repair cross-complementing-1 (ERCC-1) were useful markers to predict the efficacy of anti cancer agents including 5-fluorouracil (5-FU) and oxaliplatin for unresectable advanced colorectal cancer. In this study, we analyzed the relationship between the expression of these enzymes and the clinical significance in 49 Stage IV colorectal cancer patients who received mFOLFOX6 as a first-line treatment and evaluated the usefulness of these enzymes for predicting the efficacy of mFOLFOX6. There was no relationship between the expression of each enzyme and response rate. The progression-free survival of the patients with low TP expression was significantly longer than that of the patients with high TP expression( p<0.01). In the analysis of overall survival, the patients with low TP or low DPD expression were better than that with high TP expression or high DPD expression (p=0. 04, p=0. 04, respectively). Our results indicated that TP and DPD expression would be a useful marker to predict the efficacy of mFOLFOX6 in the patients with unresectable colorectal cancer.