Background: Published studies have demonstrated that resistin, a recently discovered adipokine, is connected to insulin resistance, type 2 diabetes mellitus, obesity, inflammation, and atherosclerotic vascular disease. A comprehensive study of the adipocytokine family and tumor pathogenesis indicates an intimate relationship between resistin and the incidence, progression, and metastasis of gastric cancer, esophageal cancer, choriocarcinoma, colorectal cancer, pancreatic cancer, and biliary tract cancer. To date, the connection between resistin and bladder cancer has not been thoroughly investigated and remains unclear. Methods: Overall, 322 patients with bladder cancer and 366 normal controls were included in the study. Two SNPs of the resistin gene, rs1862513 (also known as −420 C/G) and rs10401670 (3’UTR C/T) were genotyped across the entire cohort. Next, the association between the two SNPs and the incidence, risk factors, and prognosis of bladder cancer, were analyzed. Results: The frequency of T allele and CT/TT genotype of rs10401670 was significantly lower in bladder cancer patients (P=0.03, OR=0.79 and P = 0.018, OR = 0.68, respectively) compared to normal controls. No differences were found with regards to the rs1862513 genotype frequency and the distribution of allele frequency between the two groups. Stratified analyses showed that the CT heterozygous genotype of rs10401670 was associated with bladder cancer at an earlier age (OR=1.97, 95% CI=1.14–3.40) and the CG heterozygous genotype of rs1862513 was correlated with high incidence of bladder cancer in smokers (OR=1.73, 95 % CI=1.05–2.87). Multiple Cox regression analysis showed that for bladder cancer patients, the presence of a CG heterozygous genotype of rs1862513 was associated with a decrease in the risk of recurrence in MIBC patients (P = 0.04,OR= 0.49). Additionally, the rs1040167 CT/TT genotype (P = 0.03,OR= 2.45), especially the TT homozygous genotype (P = 0.02,OR= 3.00) was associated with high risk of death. These results indicate that the rs1040167 CT/TT and TT homozygous genotype may be a risk factor for overall survival of bladder cancer patients. Conclusions: Our results suggest that resistin genotype serves as a risk factors for the occurrence and prognosis of bladder cancer, and could be be a potential biomarker for this devastating disease.