Inflammation of gallbladder is an established risk factor for gallbladder cancer (GBC) pathogenesis. Chemokine receptors play crucial role in antitumour immunity and are involved in inflammation and pathogenesis of cancers. Present study was aimed to examine the role of CCR5 Delta32 polymorphism in conferring genetic susceptibility to GBC. Present case-control study included 144 proven GBC patients and 210 healthy controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistically significant difference was observed in distribution of CCR5+/Delta32 genotype (P = 0.028) [odds ratio (OR) = 2.850; 95% confidence interval (CI) = 1.1-7.2] and CCR5 Delta32 allele (P = 0.012) (OR = 3.145, 95% CI = 1.2-7.7) in GBC patients which was conferring high risk. Stratification of GBC patients showed significant association of CCR5+/Delta32 genotype and CCR5 Delta32 allele with GBC patients with and without gallstones. Analysis based on age of onset and gender suggested significant association of CCR5 Delta32 allele with early onset (<50 years) of the disease but only marginal influence of gender in CCR5 Delta32-mediated risk of cancer. Risk was further modulated by tobacco usage and significantly increased risk was observed in tobacco users with CCR5+/Delta32 genotype. In conclusion, CCR5+/Delta32 genotype and CCR5 Delta32 allele confer significant risk for GBC particularly in patients with early onset and tobacco usage. Role of CCR5+/Delta32 polymorphism in GBC susceptibility is independent of gallstone formation.