The innate immunity and inflammatory response plays an important role in AD pathogenesis. Recently, a wealth of information linking the activation of NLRP3 inflammasome to Alzheimer's disease (AD) pathogenesis has emerged. Considering the pivotal role of NLRP3 in the inflammatory process and in AD, we hypothesized that variations in NLRP3 gene may also affect susceptibility to AD. Three selected functional single-nucleotide polymorphisms (SNPs) in NLRP3 gene (rs2027432, rs10754558, rs35829419) were genotyped in 1133 late-onset AD (LOAD) patients and 1159 healthy controls in a large Northern Han Chinese population. Among them, the 5'-flanking rs2027432 polymorphism seemed to be most associated with LOAD risk even after adjusting for age, gender, and ApoE ε4 status. For rs10754558, the genotype frequency differed significantly only in ApoE ε4 carriers. On the other hand, the minor A allele of rs35829419 (Q705K) polymorphism appeared to exert a protective effect against the development of LOAD. Our data support the notion that genetic variation in NLRP3 gene may contribute to LOAD risk in Northern Han Chinese.