To screen differentially expressed proteins in excessive heat “shanghuo” serum and provide a scientific basis for in-depth study on the mechanism of excessive heat “shanghuo”. Methods:Serum proteins were detected by relative and absolute quantitative isotope labeling (iTRAQ), and bioinformatics analysis (GO, STRING) was used to screen the proteins that were significantly different between the normal fever group and normal non-lit group subjects. Results:Compared with the normal control group, 49 differentially expressed proteins were screened by excessive heat “Shanghuo” group, with 22 up-regulated and 27 down-regulated. Apolipoprotein C3 (Apo C3), lactate dehydrogenase (LDH), and vitamin K-dependent protein S (PROS1) were significantly up-regulated while Apo A4, SOD3 and the plasminogen activator inhibitor 1 (PAI-1) and so on were significantly down-regulated. Conclusion:The abnormal lipid metabolism and glycolytic abnormality in the “shanghuo” crowd are closely related to the occurrence of oxidative stress and inflammation, and the coagulation function is decreased, leading to easily bleeding. The differential proteins screened can provide references for biological foundation of basic research on “shanghuo”.