Apolipoprotein E (APOE), translocase of outer mitochondrial membrane 40 homolog (TOMM40) and apolipoprotein C-I (APOC1) may extend lifespan by marked delay or escape from age-related diseases. This study aimed to elucidate the association of human longevity with genetic variations in TOMM40/APOE/APOC1 region in a Chinese population. Ten tag single-nucleotide polymorphisms (SNPs) in the TOMM40/APOE/APOC1 region were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. Of the 10 SNPs, rs7254892 in 5' upstream of TOMM40 showed significant association with human longevity (G/A-A/A vs G/G: odds ratio (OR)=1.59, 95% confidence interval (CI)=1.20-2.09, P=0.0011, Bonferroni corrected P (Pc)=0.033). The haplotype analysis suggested that individuals carrying the haplotype A-A-A-A-T-A-T-G-C-A (rs7254892-rs157580-rs2075649-rs2075650-rs157582-rs8106922-rs1160985-rs405697-rs439401-rs445925) tended to have longer lifespan than those carrying the most common haplotype G-G-A-A-C-A-C-A-T-G (OR=1.59, 95% CI=1.19-2.12, P=0.0018, Pc=0.0216). These findings indicated that variants in TOMM40/APOE/APOC1 region might be associated with human longevity. Further studies are needed to identify the causal genetic variants influencing human longevity.