Abstract: Objective To analyze the quantitative results of serum differential proteins in osteoporosis patients and healthy people by isobaric tag for relative absolute quantitation(iTRAQ)technology, and to screen and identify the specific serum protein markers for early diagnosis of osteoporosis. Methods Totally 24 serum samples from healthy people and 24 serum samples from senile patients with osteoporosis were collected. The quantitative and qualitative analysis of protein was carried out in each group by iTRAQ technology, and the differences of proteomics in each group were compared. The specific proteins with significant difference(difference multiple>1.2, P<0.01)were screened. By consulting uniport database and related literatures, the characteristics of specific proteins and their correlations with osteoporosis were analyzed to preliminarily identify specific serum protein markers for early diagnosis of osteoporosis. Results A total of 31 osteoporosis-related differential proteins were screened by iTRAQ technology, of which 8 proteins were up-regulated and 23 proteins were down-regulated. EphA4, keratin(KRT)and osteoclast stimulating factor 1(OSTF1)were selected as potential biomarkers of osteoporosis. Conclusion According to the results of ingenuity pathway analysis(IPA)and the biological and physiological functions of each differential protein, three differential proteins of EphA4, KRT and OSTF1 are further screened and identified as potential protein markers for early diagnosis of osteoporosis.