The incidence rate for bladder cancer has been increasing in many countries, and bladder cancer is the most common urinary cancer in China. We explored the association of single-nucleotide polymorphisms in DNA repair genes with bladder cancer. The hypothesis is that the xeroderma pigmentosum complementary group D (XPD) 156-22541C-->A and 751-35931A-->C polymorphisms are associated with the risk of bladder cancer. In a population-based case-control study, 215 patients with newly diagnosed bladder transitional cell carcinoma and 245 cancer-free controls/healthy subjects (frequency-matched by the age and sex) were genotyped. These two polymorphisms were studied using the polymerase chain reaction restriction fragment length polymorphism method. We found that the A allele of XPD Arg156Arg (C22541A) and the C allele of XPD Lys751Gln (A35931C) is associated with increased risk of bladder cancer (adjusted odds ratio = 1.54 and 95% confidence interval = 1.19-2.01, 1.65, and 1.12-2.73, respectively). Smoking is also a risk factor in the etiology of bladder cancer, but alcohol intake is a protective factor during the development of bladder cancer. These two XPD polymorphisms may play an important role in the etiology of bladder cancer in the southeastern Chinese population.