Accumulating evidence suggests that inflammatory process may play a role in bladder carcinogenesis. However, the exact mechanisms of how the inflammatory factors associate with bladder cancer risk are still unknown. In this study, we explored whether polymorphisms (i.e. IL-4 C-590T, IL-4R Ile50Val, IL-4R Ser478Pro, IL-4R Gln551Arg, IL-13 C-1055T and IL-13 Arg130Gln) of IL-4, IL-4R and IL-13 genes predicted Chinese bladder cancer risk in 817 bladder cancer and 1,141 controls. Genotyping was performed by using the TaqMan method. We did not find any overall association between these single nucleotide polymorphisms (SNPs) and bladder cancer susceptibility in a Chinese population. However, in the classification and regression tree (CART) analysis, we found that carriers of IL-13 C-1055T variant genotype in smokers had a 2.57-fold increased bladder cancer risk with a 55% patient rate (OR = 2.57; 95% CI = 1.93-3.43), comparing with non-smokers. Similar result was also observed in combination of IL-13 C-1055T and IL-13 Arg130Gln in smokers. By multifactor dimensionality reduction (MDR) analysis, the best interaction model was the two-factor model that smokers with the IL-13 C-1055T genotypes were the subgroup to predict bladder cancer risk. The results suggested that the genetic variants in IL-4, IL-4R and IL-13 genes might modulate the bladder cancer risk in a Chinese population.