Background/Aims: To determine the effect of the pyridoxine for prevention of hand- foot syndrome in colorectal cancer patients with adjuvant chemotherapy using capecitabine. Methodology: Colorectal cancer patients scheduled for capecitabine chemotherapy as adjuvant setting were randomly assigned to with or without concurrent oral pyridoxine (60 mg/d) groups. Patients were monitored whether being a development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS until chemotherapy ended. Results: Sixty patients were enrolled in this study. Relative dose intensity was 89.5% in total. The median number of chemotherapy cycles to grade 2 or worse HFS was four in both groups. Grade 2 or worse HFS developed in 18 (60.0%) of 30 control patients and in 18 (60.0%) of 30 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS I was not different between the two groups. Conclusions: Pyridoxine is not effective in prevention of capecitabine-associated HFS.