【ABSTRACT】 Objective To analyze the proteins in serum of mycoplasma pneumonia and find the differentially expressed proteome with isobaric tags for relative and absolute Quantification (iTRAQ) technology. Methods The total proteins in serum samples from patients with mycoplasma pneumonia and samples of healthy controls were analyzed by eightplex iTRAQ added with strong cation exchange choematography and liquid chromatography coupled with tandem mass spectrometry. The differentially expressed proteins were identified by Mascot and GO. Results 66 differentially expressed proteins were identified. 52 proteins were upregulation and 14 proteins were downregulation. Bioinformatics analysis revealed that differential expression proteins were mainly related to the acutephase response, acute inflammatory response, oxygen transport, gas transport, hydrogen, peroxide catabolic process, cellular oxidant detoxification, blood coagulation, wound healing, coagulation, and cellular detoxification process. Among of them, there were 5 proteins significant differentially expressed, including upregulation expressed proteins SAA, CRP, HBB and APOM; downregulation expressed proteins APOC3 and GPX3. Conclusion This study finds that six kinds of protein in children with mycoplasma pneumonia play an important role in the process, promisingly as the disease clinical screening of potential biomarkers.