The objective of the study was to study the functioning and health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) and its associated factors. Consecutive SSc patients and an equal number of age- and gender-matched healthy controls were recruited for the assessment of functioning and HRQoL by the Health assessment questionnaire disability index (HAQ-DI) and Medical Outcomes Study Short Form 36 (SF-36), respectively. The extent of skin involvement of SSc was assessed by the modified Rodnan skin score (mRSS), and disease severity was assessed by the Medsger severity index. Factors associated with functioning and HRQoL in SSc patients were studied by linear regression. Seventy-eight Chinese SSc patients were studied (87 % women; age 50.2 ± 12.1 years; disease duration 7.8 ± 6.5 years; 81 % limited cutaneous subtype). The median mRSS of the patients was 8 (IQR 0-10). Patients with SSc had significantly higher HAQ-DI (0.69 ± 0.69 vs 0.04 ± 0.18; p < 0.001) but lower SF36 scores (p < 0.05 in all domains) than matched controls. Linear regression revealed that the mRSS was inversely associated with the physical component (beta = -0.39; p = 0.001) and mental component scores (beta = -0.27; p = 0.031) of the SF36 but positively correlated with the HAQ-DI score (beta = 0.51; p < 0.001) adjusted for age, sex, and disease duration. The SF36 and HAQ-DI scores also correlated significantly with the Medsger SSc severity index in the general, peripheral vascular, skin, tendon/joint, and heart domains. SSc patients had impaired physical and social functioning and poorer HRQoL than healthy individuals. The extent of skin involvement, tendon/joint contracture, damage in the heart, and peripheral vascular system were associated with poorer functioning and HRQoL.