Some studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479 normal controls from 12 cohorts of NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). 34 unrelated brain eQTLs for APOE were compiled from BRAINEAC and GTEx. We used multi-covariate logistic regression analysis to identify eQTLs interacted with APOE ε4. Adjusted for age and gender, substantia nigra eQTL rs438811 for APOE showed significantly strong interaction with APOE ε4 status (OR, 1.448; CI, 1.124-1.430; P-value = 7.94 × 10-6). APOE ε4-based sub-group analyses revealed that carrying one minor allele T of rs438811 can increase the opportunity of developing to AD by 26.75% in APOE ε4 carriers but not in non-carriers. We revealed substantia nigra eQTL rs438811 for APOE can interact with APOE ε4 and confers risk in APOE ε4 carriers only.