Many studies have showed that the serum cholesterol levels existed significant difference between Parkinson's disease (PD) patients and health controls. However, the serum cholesterol level in progressive supranuclear palsy (PSP) has not been studied. The object of this paper was to examine the levels of serum cholesterol and protein of PSP and their change in the disease progression. 57 possible PSP patients were collected in Beijing Tiantan Hospital from 2002 to 2014. The serum cholesterol and protein level of 57 patients were compared with 89 age-and sex-matched controls. In the 57 PSP patients, 12 patients have been in hospital two or more times. The data of these 12 patients were further analyzed to explore the changes of serum total cholesterol (TC) or total protein (TP) with the course of disease. Our findings showed that the serum TC and TP levels in patients were significantly lower than control. Multivariate logistics regression analysis showed that both TP and TC were independently associated with PSP. The serum protein and cholesterol levels further reduced from first hospitalization to the last time. The results implied that the serum protein and serum cholesterol might played a critical role in the development of PSP.