Background: Metabolic syndrome (MS) is a cluster of complicated disorders caused by the interactive influencing factors of heredity and environment, which predisposes to many cnacers. Results from epidemic research indicate that stress is tightly related to the pathogenesis of MS and neoplasia. This paper aims to investigate the association between psychological stress and MS with respect to the tumor necrosis factor alpha (TNF${alpha}$) and neuropeptide Y (NPY) genes in the Han and Hui ethnic groups. Methods: All subjects for this case-control study matched strict enrollment criteria (nationality, gender and age) and lived in the city of Wu Zhong of Ningxia Province in China. The enrolled group contained 102 matched pairs of Hui ethnic individuals and 98 matched pairs of Han ethnic individuals. Enrolled subjects completed the general Symptom Checklist-90 (SCL-90). The TNF${alpha}$-308G/A variant and NPYrs16147 polymorphism were detected in case (81 males, 119 females) and control (81 males, 119 females) groups by polymerase chain reaction (PCR) amplification. Results: Nine factors of the SCL-90 were found to be statistically different (p<0.05) between case and control groups. The homozygous mutant genotype (AA) and the mutant allele (A) of the TNF${alpha}$-308G/A gene were less frequently observed in the control population compared to the case group. The odds ratio (95% confidence interval) in "Allele" for MS was 2.28 (1.47-3.53), p=0.0001, while "OR" was 1.11 (0.83-1.47), p=0.15, for the NPYrs16147 gene polymorphism. Conclusions: Psychological stress has been positively associated with MS. A previous study from our group suggested there were differences in the level of psychological stress between Hui and Han ethnic groups. Furthermore, we found that the stress-related TNF${alpha}$ gene was associated with MS for both Han and Hui ethnic groups. In contrast, NPY may be a possible contributor to MS and associated cancer for the Han ethnic group.