Objective To investigate the association of circulating HER-2 level with metabolic syndrome in middle-aged and elderly population. Methods We conducted a population-based cross-sectional study with 687 participants aged 40 years or older from a community in Chongming District, Shanghai, China. Serum HER-2 levels were measured using ELISA. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel Ⅲ (NCEP ATP Ⅲ) criteria for Asian-Americans. Results After adjusting for other influencing factors, we found that the participants with metabolic syndrome (n=370) had significantly higher HER-2 level compared with the control group (n=317) ([12.4±2.3] ng/mL vs [8.2±1.6] ng/mL, P<0.001). The serum HER-2 level increased (P<0.001) with the accumulation of the metabolic syndrome components. After adjusting for potential risk factors, multiple logistic regression analysis showed that the highest quartile of serum HER-2 was associated with increased risk of metabolic syndrome, with a fully adjusted odds ratio (OR) of 1.35 (95% confidence interval [CI]: 1.14-2.31), P<0.001). Conclusion Serum HER-2 is independently associated with metabolic syndrome in middle-aged and elderly Chinese in this study.