Objective To study the methylation of Hedgehog interacting protein (HHIP) promoter region in peripheral blood in elderly patients with osteoporosis. Methods 102 cases of senile osteoporosis (SOP) patients in our hospital from July 2017 to July 2019 were selected as the observation group, and 100 cases of healthy elderly people in our hospital physical examination center were selected as the control group. The serum levels of bone metabolism markers, Ⅰtype procollagen Nterminal peptide (p1np) and insulin resistance were detected β-Osteogenic crosslinking（ β The level of cross laps and blood calcium content were measured; The mRNA expressions of HHIP, Shh, PTCH1, SMO, Gli1 and Gli2 were detected by real-time PCR. The methylation status of the promoter region of the target gene in mononuclear cells was detected by methylase method, and the expression of the target gene was detected by realtime fluorescent quantitative RT qPCR. Analyze the correlation between the above indicators.Results SHH, PTCH1, SMO and Gli -mRNAwere down-regulated in the mononuclear cells of the observation group (all P＜0.05). The HHIP mRNA was up regulated about 4 times in the mononuclear cells of the observation group (P＜0.01). The methylation level of HHIP gene promoter region in the observation group was significantly lower than that in the control group (P＜0.05). The blood calcium in the observation group was lower than that in the control group (P＜0.05), while the serum P1NP (P＜0.05) and β-CrossLaps (P＜0.05) were significantly higher than those in the control group. The methylation level of the HHIP promoter region was negatively correlated with P1NP and β-CrossLaps, with statistical significance (both P＜0.05). Conclusion The expression of Hedgehog signaling gene in peripheral blood mononuclear cells and the methylation level of HHIP have certain value in the diagnosis of osteoporosis in the elderly, its level is related to abnormal bone metabolism.