Neural precursor cell expressed, developmentally down-regulated (NEDD9) gene was a new candidate risk gene for Alzheimer disease (AD). The CC genotype of a single nucleotide polymorphism rs760678 within this gene was associated with increasing risk of AD in a large study with white population. Our study aimed to replicate the initial report in Chinese population and explore its effect on cognitive performance. A total of 262 patients with AD, 293 patients with mild cognitive impairment, and 434 cognitive intact controls were recruited in the study. The result showed that G allele had a greater risk of AD (χ2 for trend test=5.61, df 1, P=0.018). The effects were mainly observed among Apolipoprotein E (APOE) ε4 noncarriers (χ2 for trend test=4.30, df 1, P=0.038). After adjustment of sex, age, education year, and APOE ε4 status by logistic regression, significant association between NEDD9 GG genotype and AD remained [OR=2.04, 95% confidence interval (CI)=1.02-4.08, P=0.044]. The scores of Cantonese version of the Mini-mental State Examination and Alzheimer’s Disease Assessment Subscale—Cognitive subscale were associated with N polymorphism after adjusting for sex, age, education year, and ApoE ε4 status (Linear regression model, P<0.05). Our study identified rs760678 within NEDD9 gene in association with the risk of AD and cognitive performance in Chinese older persons. The fact that different alleles accounted for the risk in different population might suggest that there were ethnic group specific haplotypes that were primarily responsible for the predisposition.