Abstract: Objective To investigate the performance of high frequency ultrasound in the assessment of skin thickness in patients with systemic sclerosis (SSc). Methods The study included 82 SSc （SSc group）and 67 healthy volunteers （control group） from 2014 to 2016. The skin thickness at bilateral middle fingers and forearms, anterior chest and abdominal wall was measured using high frequency ultrasound. All the patients with SSc underwent the modified rodnan skin score (mRSS) over 17 anatomical sites by an experienced dermatologist. The differences in age, sex, height, body mass, body mass index (BMI) and skin thickness between SSc patients and healthy controls were compared. Receiver operating characteristic (ROC) curve analysis was performed to determine the performance of high frequency ultrasound in the differentiation of SSc from healthy skin, and the correlation of mRSS with skin thickness were analyzed. Results SSc patients and healthy controls shared similar demographic features (age, sex ratio, height, body mass, BMI) (P>0.05). Skin thickness values in SSc patients were increased significantly at fingers and forearms compared with healthy controls (P<0.05). The area under the curve (AUC) was 0.938，0.905，0.608，0.586，0.398，0.321 at right and left finger, right and left forearm, chest and abdominal wall. Among them, AUC>0.9 of right and left fingers can be used for diagnosis， The skin thickness cut-off value for determining the diagnosis of SSc were as follows: 1.35 mm at the right finger with 84.1% sensitivity and 95.5% specificity, 1.26 mm at the right forearm with 86.6% sensitivity and 89.6% specificity, respectively. Skin thickness increased significantly with mRSS. The correlation of total mRSS scores with total skin thickness was 0.599 (P<0.001), and the correlation of local mRSS score with local skin thickness were 0.400-0.623 (P<0.001), with the highest correlation coefficient at right finger and the lowest at abdomen. Conculusions High frequency ultrasound may reflect extent of skin involvement of SSc, and skin thickness assessed with high frequency ultrasound appeared to be highly specific and sensitive at fingers.