Background: There have been few data on the health-related quality of life (HRQOL) in patients with pneumoconiosis. HRQOL is an important aspect of daily living in patients with industrial diseases. Objectives: To investigate the HRQOL and factors that contribute to the impairment of HRQOL in patients with pneumoconiosis. Methods: 297 patients with pneumoconiosis were recruited from a community-based case registry. The HRQOL was measured with the St. George’s Respiratory Questionnaire (SGRQ). Pulmonary function, comorbidity and psychosocial variables were also assessed. Patients’ mood state was evaluated with the Geriatric Depression Scale (GDS). Results: The mean SGRQ symptom, activity, impact and total scores were 38.0 ± 19.3, 44.5 ± 21.9, 34.2 ± 17.9 and 39.4 ± 17.4, respectively. These figures were lower than those reported in patients with chronic obstructive pulmonary disease who attended chest clinics. The GDS score (r = 0.38), forced expiratory volume in 1 s predicted (FEV1% predicted;r = –0.33) and comorbidity (r = 0.21) were the most important predictors of the HRQOL. Conclusions: Besides lung functions, chest clinicians should consider the impact of mood symptoms and comorbidity on the HRQOL in the management of patients with pneumoconiosis.