Objective To study the correlation between central obesity and the difference of mRNA and protein expression of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-induced early reactive protein 14(Fn14)and downstream nuclear factor-kappa B(NF-κB)pathway in peripheral blood mononuclear cells (PBMC) in the elderly. Methods From September 2017 to May 2018,80 subjects were randomly selected from the database of cross-sectional epidemiological survey of permanent residents in agricultural and pastoral areas of Xinjiang. According to whether they had central obesity or not, they were divided into the control group (n=40) and the central obesity group (n=40). PBMC were extracted from fasting peripheral blood, and the mRNA and protein expressions of TWEAK, Fn14, inhibitor of kappa B kinase-α (IKKα), inhibitor of kappa B kinase-β (IKKβ) and NF-κBp65 were detected by quantitative real-time polymerase chain reaction and Western-blotting. SPSS 26.0 was used for statistical analysis. Data comparison between two groups was performed using t-test or χ² test, depending on data type. Correlation was analyzed using bivariate Pearson correlation analysis method. Results The mRNA expression of Fn14, IKK α, IKK β, TWEAK and NF-κBp65 in PBMC in the central obesity group was higher than that in the control group, but the difference was not statistically significant (P>0.05). The protein expression levels of Fn14, IKK α and IKK β in the central obesity group were higher than those in the control group (P<0.05), but there was no significant difference in TWEAK and NF-κBp65 protein expression between the two groups (P>0.05). Bivariate Pearson correlation analysis showed that mRNA expression of the above factors was positively correlated with TWEAK and Fn14 (r=0.472; P<0.01), Fn14 was positively correlated with IKK α and IKK β(r=0.262,0.275; P<0.05), and that IKK α and IKK β were positively correlated with NF- κBp65 (r=0.747,0.692; P<0.01). Conclusion Central obesity in the elderly in the agricultural and pastoral areas of Xinjiang is related to the high expression of Fn14, IKK α, IKK β and mRNA in peripheral blood PBMC. TWEAK/Fn14 may be involved in the occurrence and development of human obesity by regulating IKK to activate NF- κB inflammatory pathway.