Recent studies suggest that genetic factors contribute to the pathogenesis of sporadic Alzheimer's disease (sAD). Glycogen synthase kinase-3 beta (GSK 3β) is an important molecule which regulates tau phosphorylation and neurofibrillary tangles formation. GSK 3β gene may be a potential candidate gene for the risk of sAD. To investigate the association of the polymorphisms in GSK 3β gene with sAD, we conducted a case-control study in a southern Chinese Han cohort including 302 sAD patients and 315 control participants. Four single nucleotide polymorphisms (SNPs) (rs3732361, rs56728675, rs60393216, and rs334558) within the promoter region of GSK 3β gene were selected and genotyped with a polymerase chain reaction-ligase detection (PCR-LDR) method. Logistic regression was used to analyze the association between target SNPs and the risk of sAD. After adjusting for age, sex, and APOE ε4 status, no association was revealed between these SNPs and sAD (P > 0.05). The SNPs in the selected regions of GSK 3β gene are unlikely to confer the susceptibility of sAD in southern Chinese Han population. Further studies with a larger sample size and different ethnic populations are needed to reveal the role of SNPs of GSK 3β gene in the pathogenesis of sAD.