Objective: To screen specific modification proteins in peripheral blood of patients with Trauma-induced osteonecrosis of the femoral head (TIONFH) and further explore the epigenetic mechanism of the occurrence of TIONFH. Methods:Three peripheral blood samples were collected from patients with TIONFH (experimental group) and traumatic patients without necrosis (control group),, and total protein was extracted. The levels of phosphorylation, acetylation, ubiquitination and succinylation of peripheral blood protein were investigated by panantibody, and the modified types with obvious changes in TIONFH were determined. By combining TMT labeling, HPLC classification technology, acylated peptide enrichment technology and quantitative proteomics technology based on mass spectrometry, the quantitative omics of TIONFH specific modification was further studied, and the proteins corresponding to the screened difference sites were analyzed by clustering and protein-protein interaction. Results: Compared with the control group, the level of acetylation in peripheral blood of the experimental group was significantly different. Further, acetylation quantitative histological analysis showed that 145 sites of 93 proteins contained quantitative information, among which P < 0.05 was considered statistically significant. In the experimental group, there were 10 up-regulated acetylation sites, including 8 proteins and 2 down-regulated acetylation sites with 2 proteins. Conclusion: There are significant changes in the acetylation level of peripheral blood protein in patients with TIONFH, and the screened differentially modified sites and proteins can be used as candidate molecular markers of TIONFH.