To investigate whether the variations of genes encoding pro-inflammatory cytokines is associated with longevity in Uyghurs in Xinjiang. A total of 240 individuals aged ≥90 years from Xinjiang Uyghur Autonomous Region were enrolled between 1999 and 2012 as the longevity group, 92 unrelated individuals from the same area who died naturally at the age of 59-73 in the same period were selected as the control group. Seven single nucleotide polymorphisms (SNPs) of 4 genes (tumor necrosis factor (TNF)-α(rs1800629), IL-6(rs1800796, rs10499563), C-reactive protein (CRP) (rs2808630, rs1205) and IL-1β(rs1143623, rs16944)) were genotyped. Logistic regression was applied to assess the association between each individual SNP and longevity in case-control analyses. The distribution of C allele of rs1800796 in the longevity group (0.298) was lower than that in the control group (0.435) with statistical significance (P=0.001). The distributions of the other 6 genetic variations between the longevity group and the control group showed no statistically significant differences (all P>0.05). CT genotype of rs1800796 was positively associated with longevity (Padd=0.002, OR=1.983, 95%CI: 1.296-3.023), while no significant association was noted between other genotypes and longevity. SNP of rs1800796 of IL-6 gene may be significantly associated with longevity in Uyghurs in Xinjiang. CT genotype of rs1800796 is significantly associated with longevity. C allele of rs1800796 may be a negative factor for longevity.