The aim of this cross-sectional study was to compare health-related quality of life (HRQOL) of Russian hemodialysis (HD) patients with the general population and international data, and to determine factors influencing HRQOL. One thousand forty-seven HD patients from 6 dialysis centers were studied (576 male, age 43.5±12.5 years, HD duration 55.0±47.2 months). Health-related quality of life was evaluated by SF-36. Self-appraisal Depression Scale (W. Zung), State-Trait Anxiety Inventory, and Level of Neurotic Asthenia Scale were used. Hemodialysis patients scored significantly lower than the general Russian population in the majority of SF-36 scales. The only exception was the Mental Health score, which was even better than the general population. The Mean physical component score (PCS) of HD patients was 36.9±9.7, and the mental component score was (MCS) 44.2±10.5. In multiple linear regression analysis, increasing age, HD duration, depression level and number of days of hospitalization in the past 6 months were significant independent predictors of low PCS along with a low level of serum albumin. Advancing age was also a predictive factor for low MCS along with increase of HD duration, depression level, trait anxiety, and level of asthenia. As far as we know, this is the first study to report on HRQOL of a large sample of Russian HD patients performed using SF-36. Compared with the general population, Russian HD patients had significantly lower scores on the majority of SF-36 scales, especially in the physical domain. The mean PCS and MCS were comparable with European data for HD patients. A number of demographic, clinical, and psychological variables affect HRQOL.