Background. Hand-foot syndrome (HFS) is a common systemic skin toxicity syndrome caused by chemotherapy agents. However, there is no uniform clinical treatment for HFS. It is reported that pyridoxine (vitamin B6) can be used to prevent HFS, but the evidence is insufficient. Aim. To determine whether pyridoxine can be used to prevent HFS caused by chemotherapy agents. Methods. Literature database searches were performed on PubMed, Web of Science, Embase, Cochrane Library and China National Knowledge Infrastructure. The efficacy of pyridoxine was evaluated by the incidence of HFS (any grade) or severe HFS (grade ≥ 2). Results. Fourteen studies involving 1570 patients were included in this meta-analysis. There were no significant differences between the pyridoxine and control groups in the prevention of HFS (OR = 0.84, 95% CI 0.67-1.05, P = 0.09) or in the incidence of grade ≥ 2 HFS (OR = 0.87, 95% CI 0.70-1.09, P = 0.39, respectively). The subgroup analysis of pyridoxine dose also showed no significant difference between the two groups in preventing HFS grade ≥ 2 (OR = 0.79, 95% CI 0.62-0.99, P = 0.30). Conclusions. We did not find adequate evidence to support the idea that the use of pyridoxine can prevent HFS and reduce the incidence of HFS grade ≥ 2. However, the preventive use of pyridoxine might have a tendency to reduce the incidence of HFS.