Background: Patients on hemodialysis (HD) generally display a significant decrease in the quality of life owing to comorbidities, malnutrition, and inflammation.Methods: In this multicenter prospective study, the Sf36 (short form with 36 questions scored between 0 and 100) and relevant demographic data and comorbidities (charlson comorbidity index); nutritional factors, and C-reactive protein (CRP) were evaluated in 416 HD patients in September 2012. Hospitalization and mortality were assessed in a median of a 28 month follow-up.Results: The Sf36 score in survived patients was 53.619.3 versus 41.622.4 in the non-survived patients (P<0.001). There were significant adjusted inverse correlation between the Sf36 score and age (r=-0.14, P=0.005), diabetes (r=-0.13, P=0.009), CCI (r =-0.24, P<0.001), serum CRP level (r=-0.13, P=0.03), serum iPTH level (r=-0.19, P<0.001), and also significant adjusted direct correlation with serum albumin (r=0.15, P=0.003), and serum creatinine (r=0.12, P=0.04). In Cox proportional hazard models adjusting for age, gender, dialysis vintage, diabetes and serum albumin, the hazard ratio of death for every 10 unit decrease in Sf36 score was 1.10 (95% CI: 1.04 - 1.22; P=0.006). The adjusted hazard ratio for quintiles of serum albumin as3.60, >3.60 - 3.85, >3.85 -4.00, >4.00 - 4.20, >4.20 (reference) g/dL was respectively 3.69 (1.98 - 6.89), 2.08 (1.10 - 3.94), 1.91 (0.97 - 3.85), 1.10 (0.76 - 1.49). Serum albumin revealed a strong association with mortality such that hazard ratio for every 1 g/dL decrease in serum albumin was 6.28 (95% CI: 3.80 - 10.42; P<0.001).Conclusions: In patients with hemodialysis, Sf36 shows significant association with serum albumin, comorbidities, inflammation, and clinical outcome.