The aim of the present study was to evaluate the association and prediction of dihydropyrimidine dehydrogenase gene () polymorphisms and the risk of 5-fluorouracil (5-FU) severe toxicity in cancer patients. A meta-analysis of the published literature was conducted to summarize evidence for gene polymorphisms associated with an increased risk of severe 5-FU toxicity in patients with cancer from an Asian population. Relevant literature was identified using the PubMed and Cochrane databases on April 11, 2014. Combined risk ratios and 95% confidence intervals (CIs) were calculated in a fixed-effects model. A total of 5 clinical studies were retrieved in the meta-analysis, including 764 cancer patients with gene polymorphisms who received 5-FU-based chemotherapy. Overall, gene polymorphisms were associated with the increased risk of 5-FU severe toxicity [risk ratio=2.54 (2.15-3.00); 95% CI, 19.46-84.57; P=0.0001]. In conclusion, the present meta-analysis suggested that polymorphisms of several gene polymorphisms are associated with an increased risk of severe toxic response to 5-FU.