Abstract: OBJECTIVE To study the expression of Hedgehog signaling pathway protein in the skin lesions of patients with condyloma acuminata（CA）, and its clinical significance. METHODS 158 patients with CA in department of dermatology of Wuwei People's Hospital from Feb 2019 to Feb 2021 were selected as study subjects. The lesions and adjacent healthy skin were taken, and the human papillomavirus（HPV） and expression levels of ligand protein Hh, receptor protein Ptch-1, transmembrane protein Smo, and downstream transcription factor Gli-1 were detected. RESULTS Among 158 patients with CA, 93 cases of single HPV infection accounted for 58.86%, and 65 cases of multiple HPV infection accounted for 41.14%, 53 cases of high-risk HPV infection accounted for 33.54%, 67 cases of low-risk HPV infection accounted for 42.41%, and 38 cases of high and low risk mixed infection accounted for 24.05%. The expression levels of Hh, Smo, Ptch-1 and Gli-1 in the skin lesions of patients with CA were significantly higher than those in the normal skin（P＜0.05）. The expression levels of Hh, Smo, Ptch-1 and Gli-1 in the skin lesions of patients with high and low risk mixed infection were significantly higher than those of patients with simple high-risk infection and patients with low-risk infection, and the expression levels of Hh, Smo, Ptch-1 and Gli-1 of patients with high-risk HPV infection were significantly higher than those of patients with low-risk HPV infection（P＜0.05）. The expression levels of Hh, Smo, Ptch-1 and Gli-1 in CA patients with relative light units/cut off（RLU/CO） of 100～1 000 and ＞1 000 were significantly higher than those in patients with RLU/CO of 1～10 and of 10～100, and the expression levels of Hh, Smo, Ptch-1 and Gli-1 in patients with RLU/CO＞1 000 were significantly higher than those of patients with RLU/CO of 100～1 000（P＜0.05）. High-risk HPV infection, mixed infection with high and low risk, RLU/CO of 100～1 000 and RLU/CO＞1 000 were important influencing factors for the increase of Hh expression level（P＜0.05）. CONCLUSION The expression levels of Hedgehog signaling pathway-related proteins including Hh, Ptch, Smo and Gli1 in the skin lesions of patients with CA were significantly increased, and were closely related to high-risk and high-load HPV infection, which might play an important role in the process of malignant diseases causing by HPV infection.