Inflammatory bowel disease is a multifactorial disease. Oxidative stress has been thought to be one of etiologic factor for inflammatory bowel disease. The genes superoxide dismutase (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress. The purpose of the present case-control study with 134 patients with ulcerative colitis (UC) and 125 healthy controls was to determine whether polymorphisms of these genes, the NQO1 C609T and the SOD2 Ala-9Val, are associated with the risk of UC and influence the clinical characteristics. These polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphisms and direct sequencing. In patients showing steroid resistance, the number with the NQO1 T/T genotype was significantly higher than other genotypes (odds ratio 9.45, 95% confidence interval 2.46-41.6, p = 0.002). In the patients whose onset of UC was age 20 years or younger, more patients had SOD2 T/T genotype than the other genotypes (odds ratio 6.46, 95% confidence interval 0.82-51.0). No association between these polymorphisms and UC risk was apparent. The NQO1 C609T polymorphism may influence steroid resistance of UC patients, while the SOD2 Ala-9Val polymorphism may influence age of onset of UC. Oxidative stress may influence the clinical features of UC.