Decreased expression due to genetic variations in complement receptor 1 (CR1) on erythrocytes might result in reduced clearance of immune complexes, conferring interindividual variation for gallbladder cancer (GBC) susceptibility. We studied role of CR1 (A(3650)G RsaI and Intron 27 HindIII) polymorphisms in gallstone disease and GBC in north Indian population. Study included 185 GBC patients, 185 gallstone patients and 200 controls. Genotyping was done by PCR-RFLP. Result showed GG genotype and G allele of CR1 A(3650)G RsaI were conferring significant risk for GBC [(P = 0.022; OR = 1.94; 95% CI = 1.1-3.4) and (P = 0.035; OR = 1.35; 95% CI = 1.0-3.8) respectively]. Also, comparison of GBC patients with gallstone patients showed increased risk for GBC in presence of GG genotype and G allele GBC (P = 0.048; OR = 1.74; 95% CI = 1.0-3.0) and (P = 0.027; OR = 1.39; 95% CI = 1.0-1.8) respectively. No association of CR1 A(3650)G RsaI polymorphism was observed when gallstone patients were compared with controls. CR1 Intron 27 HindIII polymorphism was not associated with GBC and gallstone susceptibility. Haplotype analysis showed increased risk of GBC in presence of G,L haplotype (P = 0.046; OR = 1.35: 95% CI = 1.0-1.8). Subgroup stratifications on basis of gender and gallstone status showed GG genotype of CR1 A(3650)G RsaI polymorphism imparted high risk for GBC in females (P = 0.043; OR = 1.99: 95% CI = 1.4-3.9). Also there was increased risk for GBC in presence as well as absence of gallstones (OR = 1.85 and 1.76 respectively), but it was not statistically significant. We conclude that CR1 A(3650)G RsaI polymorphism plays an important role in conferring genetic susceptibility to gallbladder cancer GBC in north Indian population.