Programmed cell death 6 (PDCD6) has recently been found dysregulated in tumors of various origin. The aim of this study is to explore the association between PDCD6 genetic polymorphisms and susceptibility to bladder cancer and survival of patients with bladder cancer. Two tag SNPs of PDCD6, rs3756712 and rs4957014, were genotyped in 332 patients with bladder cancer and 509 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and correlated with patients' survival. The frequencies of G allele and GG genotype of rs3756712 in patients were significantly lower than that of controls (P = 0.001, odds ratio [OR] = 0.68 for G allele; P = 0.024, OR = 0.53 for GG genotype in the recessive genetic model, respectively). The GT genotype of rs4957014 was associated with decreased susceptibility to bladder cancer in the overdominant genetic model (P = 0.023, OR = 0.72). Kaplan-Meier curves revealed a significant higher risk for death in superficial bladder cancer patients harboring GG homozygous of rs3756712 (P < 0.001), and an increased risk for recurrence in invasive bladder cancer patients carrying GT heterozygous of rs4957014 (P = 0.04). Multiple Cox regression analysis identified rs3756712 GG genotype as an independent prognostic factor for death in superficial bladder cancer patients (hazard ratio [HR] = 5.11, P = 0.01), and rs4957014 GT genotype as an independent prognostic factor for recurrence in invasive bladder cancer patients (HR = 1.93, P = 0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death.