Abstract:[Background] As a substitute of Cordyceps sinensis, Cordyceps militaris has similar pharmacological activities with Cordyceps sinensis. It is rich in protein and amino acids, which is usually used as an important index to measure the nutritional value of fungi. It has become a research focus to isolate and purify proteins or peptides with potential clinical application value from Cordyceps militaris. [Objective] The protein composition of fruiting bodies of wild and commercial strains of Cordyceps militaris in Shenyang were detected, and the differences of protein types, quantities and functions under the same cultivation conditions were analyzed, which provided the proteomic data basis for further study and identification of protein for medicinal use and targeted domestication of northern caterpillar in Shenyang area. [Methods] Wild Cordyceps militaris strains were collected from Qipan Mountain of Shenyang. Fruiting bodies of wild and artificially cultivated Cordyceps militaris strains were obtained by tissue isolation and liquid fermentation respectively at the same time. The quantitative proteome of fruit body samples from wild and commercial sources was studied by non-standard quantitative technology liquid chromatography-mass spectrometry after protein extraction and trypsin enzymolysis. [Results] A total of 9 233 specific peptide fragments and 1 923 proteins were identified, including 1 163 quantifiable proteins. 214 proteins were up-regulated and 181 proteins were down-regulated in fruit bodies cultured from wild sources. After functional enrichment analysis, these differential proteins were mainly involved in energy production/conversion, amino acid transport/metabolism and antioxidant function. Under the same nutritional conditions, the expression of protein related to energy metabolism and amino acid metabolism of wild-type strains was higher than that of commercial strains, and the expression of an important antioxidant protein (Gene Name:ISF_02112) from wild cultivated strains was much higher than that in commercial strains (fold change>9). There were 22 differentially expressed proteins related to both antioxidant and metabolic functions. [Conclusion] Some excellent biological characteristics of wild Cordyceps militaris in Shenyang can be preserved by proper artificial cultivation. The fruiting bodies cultivated by the two strains have rich and excellent antioxidant proteins, and the antioxidant capacity of fruiting body proteins is related to their overall metabolic capacity. The results of this study provide the basis of proteomics data for further study and identification of the herbal protein and targeted domestication of Cordyceps militaris.