Background: Health-related quality of life (HRQL) in the general population of Kazakhstan has never been characterized. We constructed this population-based study of the largest city in Kazakhstan, Almaty with the aim to quantitatively assess HRQL and ascertain whether occupation and lifestyle are associated with HRQL in this population. Methods: In a random sample (N = 1500) of general population in Almaty (median age 49 (interquartile range 28) years, 50% women), we collected data on demographics, socioeconomic status, lifestyle, lifetime occupational history and general HRQL using SF-8 instrument. The association of demographic and occupational predictors with HRQL was tested in multiple regression models. Results: No occupational associations were found for physical component score in the models adjusted for age, sex, income, cigarette and waterpipe smoking, electronic cigarette use, physical activity, alcohol and exposure to secondhand smoke. Ever being a manager (β − 1.63 (95% confidence interval (CI) − 2.92; − 0.34)), a welder (β − 5.11 (95% CI − 8.77; − 1.46)) and a secretary (β − 5.06 (95% CI − 8.56; − 1.56)) for one year or more was associated with poorer mental component score in the models adjusted for age, sex, income, cigarette smoking, physical activity and each other. Age, income and physical activity were independent predictors of both physical and mental components. Conclusions: Occupational history is associated with HRQL in the general population in Almaty, Kazakhstan, but the mechanism explaining this association should be further elucidated. © 2021, The Author(s).