Objective: To understand the health-related quality of life for patients of pneumoconiosis combined with tuberculosis and its main influencing factors. Methods: This was a cross-sectional study, and 951 patients of pneumoconiosis combined with tuberculosis from the pneumoconiosis survey in 27 provinces and autonomous regions in China from December 2017 to December 2021 were selected for the study. The nonparametric Mann-Whitney test and the Kruskal-Wallis H test were used to compare the health utility values, and multiple linear regression was used for multifactor analysis. AMOS 24.0 was used to establish a structural equation modeling. Results: The mean age of 951 patients of pneumoconiosis combined with tuberculosis was (59.3±12.4) years. The main types were silicosis combined with tuberculosis (62.2%, 591/951) and coal-worker's pneumoconiosis combined with tuberculosis (34.9%, 332/951), and other type pneumoconiosis-combined tuberculosis was 2.9% (28/951). The proportion of patients with stage Ⅰ, Ⅱ, Ⅲ, and unstaged clinical diagnosis was 27.4% (261/951), 26.6% (253/951), 32.5% (309/951) and 13.5% (128/951), respectively. 63.3% (602/951) of study participants suffered from other chronic diseases, and the percentage of patients combined the number of chronic diseases with 1, 2, and more than 3 respectively were 24.1% (229/951), 16.3% (155/951) and 22.9% (218/951). The median and quartiles of health utility values and the mean±standard deviation of self-rating scores of patients of pneumoconiosis combined with tuberculosis were 0.562 (0.482, 0.766) and (53.7±18.4), respectively, which were lower than patients of pneumoconiosis without tuberculosis (Z=-11.29, P<0.001; t=8.97, P<0.01). The health utility values and self-rating scores for patients of pneumoconiosis combined with tuberculosis were significantly different between urban and rural areas (Z= -2.22, P=0.027; t=4.85, P<0.01). Pain/discomfort was the most frequently reported problem in the five-dimensional distribution of problems, followed by daily activities and anxiety/depression, and the difference in the percentage reported by anxiety/depression between urban and rural areas was significant (χ(2)=30.28, P<0.01). The results of multiple linear regression showed that the survey area, body mass index, education level, age, employment status, annual personal income, stage of pneumoconiosis, number of multi-morbidities, hemoptysis, acute exacerbation of symptoms in two-week, social support and minimum living standard were the main influences on the health utility values of the patients of pneumoconiosis combined with tuberculosis (P<0.05). The results of structural equation model showed that economic security and health status directly affected the health-related quality of life among patients of pneumoconiosis combined with tuberculosis and played a chain-mediating effect in the influence of socioeconomic status on the health-related quality of life among patients of pneumoconiosis combined with tuberculosis. Conclusion: Health-related quality of life was poorer in patients of pneumoconiosis with tuberculosis, with pain and discomfort and anxiety/depression problems being more pronounced, and economic status and health status played multiple mediating roles in the influence of general socio-demographic characteristics on quality of life in pneumoconiosis.