OBJECTIVE To investigate the association between genetic polymorphism of UGT1A7 and susceptibility of bladder cancer. METHODS Based upon a case-control study, UGT1A7 polymorphisms were determined by the semi-nested polymerase chain reaction (SN-PCR) and allele-specific polymerase chain reaction (AS-PCR) in 208 cases with bladder cancer and 205 non-tumor controls. Risks were evaluated by unconditional logistic regression analysis. RESULTS The frequency of variant homozygous genotype in cases (20.7%) was higher than that in controls (12.2%) and the difference was statistically significant [P < 0.05, OR = 2.16 (1.18 - 3.96)]. The frequency of variant allele (*)3 in cases was higher than that in controls (27.9%, 20.5% respectively) and the difference was statistically significant [P = 0.009, OR = 1.56 (95%CI: 1.12 - 2.18)]. The smokers with variant homozygous and heterozygous genotypes showed an increased risk of bladder cancer compared with those with wild genotype [2.16 (95%CI: 1.07 - 4.36), 2.64 (95%CI: 1.02 - 6.80) respectively]. There was no association between the UGT1A7 polymorphisms and the pathological grade and clinical stage of bladder cancer (both P > 0.05). CONCLUSIONS The genetic polymorphisms of UGT1A7 are associated with the susceptibility of bladder cancer and have interactions with smoking in bladder carcinogenesis.