Objective · To investigate the relation between FOS gene and Alzheimers disease (AD), and the relation between tag single nucleotide polymorphism (SNP) in rs1063169 and AD in Han Chinese people. Methods · The difference in FOS gene in various brain regions between AD patients and healthy people was studied using Alzdata website, and protein-protein interaction (PPI) network among FOS protein and 28 proteins encodedAD-related susceptibility genes was constructed through String database into explore whether FOS gene was associated with AD in these known database. Then, 715 AD patients and 760 healthy controls Southwest and East China were collected to analyze tag SNP rs1063169SNaPshot assay. Results · The cross-platform normalized data on Alzdata showed that FOS gene in AD patients expressed differently in entorhinal cortex (P0.003) and hippocampus (P0.001) compared with healthy people. PPI network found out that FOS protein had interactions with 4 proteins encodedAD-related susceptibility genes, which were apolipoprotein E (APOE), clusterin (CLU), β-amyloid precursor protein (APP), and protein-tyrosine kinase 2β (PTK2B). However, there was no significant difference in the frequencies of genotypes and alleles in rs1063169 between the AD cases and the healthy controls (P>0.05). Conclusion · There is differential of FOS in the entorhinal cortex and hippocampus of AD patients and healthy people, and FOS protein may have effects on the development of AD through the interaction with proteins encodedAD-related susceptibility genes, but no relation was found between rs1063169 polymorphism and AD in the collected Han Chinese people.