Objective To detect the serum Dickkopf 1 (DKK1) protein level in patients with osteonecrosis of the femoral head, and explore its significance in early diagnosis and disease monitoring of osteonecrosis. Methods Sixty-seven patients with femoral head necrosis (ARCO stage: 13 cases in stage II, 27 cases in stage Ⅲ, and 27 cases in stage IV) who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from May to November 2016 were selected as the experimental group and 67 others who were normal from the Physical Examination Center of the same hospital in the same period were randomly selected as the control group. Enzyme-linked immunosorbent assay was used to detect the serum concentration of DKK1 protein in the two groups, and then the differences in serum DKK1 protein concentrations between the two groups and among the patients with different ARCO stages as well as different causes of femoral head necrosis in the control group were compared and analyzed. Results The serum DKK1 protein concentration in the experimental group was higher than that in the control group (P < 0.05). The serum DKK1 protein level before collapse was higher than that after collapse (P < 0.05). ROC curve indicated that serum DKK1 protein level had certain sensitivity (57.40%) and significant specificity (100%) in the diagnosis of femoral head necrosis collapse. There was no significant difference in serum DKK1 protein concentration between the patients with different causes (P > 0.05). The serum DKK1 protein concentration was significant different among the patients with different ARCO stages (P < 0.05), and serum DKK1 protein concentration had a positive correlation with ARCO stages (P < 0.05). Conclusions Serum DKK1 protein level is closely related to the progression of osteonecrosis of the femoral head. It has certain reference significance to early diagnosis of femoral head necrosis and monitoring the disease procession. It can be used as one of the reference indicators for clinical diagnosis and treatment of the disease.