In this study, we aimed to evaluate the factors associated with disability and quality of life (QoL) in Turkish patients with systemic sclerosis (SSc). Between January 2018 and January 2019, a total of 256 SSc patients (20 males, 236 females; mean age: 50.9±12.4 years; range, 19 to 87 years) who were diagnosed with SSc were included in the study. Disability and health-related QoL (HRQoL) were evaluated by the Health Assessment Questionnaire (HAQ), scleroderma HAQ (SHAQ), Duruöz Hand Index (DHI), and Short Form-36 (SF-36). Linear regression analysis methods were used to describe factors associated with disability and QoL of the patients. All disability scores were higher and HRQoL scores were lower in diffuse cutaneous SSc patients compared limited cutaneous SSc, and differentiations were significant (p=0.001 and p=0.007). In multiple regression, pain (VAS) was the strongest predictor for high disability and low QoL scores (p<0.001) as HAQ (β=0.397, 0.386, 0.452), SHAQ (β=0.397, 0.448, 0.372), DHI (β=0.446, 0.536, 0.389), PCS (β=-0.417,-0.499, -0.408) and MCS (β=-0.478, -0.441, -0.370) in combined, lcSSc and dcSSc patients respectively. The factors associated with high disability and low QoL scores were forced vital capacity for HAQ (β=-0.172, p=0.002) and SF-36 PCS (β=0.187, p=0.001); disease duration for HAQ (β=0.208, p<0.001), DHI (β=0.147, p=0.006), and SF-36 PCS (β=-0.134, p=0.014); 6-minute walk test for HAQ (β=-0.161, p=0.005) and SF-36 PCS (β=0.153, p=0.009); and modified Rodnan skin score for SHAQ (β=0.250, p<0.001) and DHI (β=0.233, p<0.001) in SSc patients. Diffusing capacity of the lungs for carbon monoxide for HAQ (β=-0.189, p=0.010) and SHAQ (β=-0.247, p=0.002); erythrocyte sedimentation rate for DHI (β=0.322, p<0.001); age for SF-36 PCS (β=-0.221, p=0.003) and body mass index for SF-36 PCS (β=-0.200, p=0.008) and MCS (β=-0.175, p=0.034) were the other variables associated with high disability or low QoL scores in SSc subsets. Clinicians should consider the management of the pain and its sources as a key to improve better functional state and quality of daily life in SSc.