Chemokines are small inducible pro-inflammatory cytokines. In the present study, we tested association of chemokine single nucleotide polymorphisms (SNPs) viz., CCR5∆32, CXCL12G801A and CXCR2C1208T genes in bladder cancer (BC) patients and normal healthy controls of north Indians. Genotyping of the above SNPs were done in 200 BC cases and 200 healthy controls, using RFLP and amplification refractory mutation system-polymerase chain reaction methodology. A significant association was found in CXCL12G801A with BC risk. In case of CXCL12G801A polymorphism, the heterozygous (GA) genotype showed significantly high risk (p < 0.001, odds ratio (OR) = 2.72), whereas A allele carrier (GA + AA) also showed risk with BC (p < 0.001, OR = 2.44). In CXCR2C1208T polymorphism, the variant genotype (TT) showed significant risk for BC (p = 0.028, OR = 1.58). The variant allele (T) of CXCR2C1208T polymorphism was found to be associated with BC risk (p = 0.003, OR = 1.29). Interestingly, smoking was also found to modulate 1.16-fold risks for BC in case of CXCR2C1208T, variant genotype (TT). Upon analyzing the gene-gene interaction between CXCR2C1208T and CXCL12G801A, the combination CT-GA showed 4-fold risk for BC (p = 0.009). Our results indicated that polymorphism in CXCR2C1208T and CXCL12G801A showed high risk for BC in north Indian population. However, CCR5∆32 exhibited no association. Study with large sample size and diverse ethnicity are required to validate these observations.