Abstract Background and Aims Frailty is common among hemodialysis (HD) patients. Its assessment is usually based on clinical criteria. In the present work, we evaluated the interest of combining clinical frailty score and biomarkers to predict mortality of chronic HD patients. Three biomarkers were assessed: myostatin, insulin-like growth factor-1 (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S) Method Prevalent HD patients were enrolled from September 2016 to October 2017 in two centers in Liège, Belgium in this observational prospective study and followed up for 5 years. Myostatin, IGF-1 and DHEA-S levels were measured at baseline. Frailty was assessed using Fried's five points frailty score (≥3 indicates frailty). The ability to predict mortality was assessed by calculating areas under the curve (AUC). AUCs were compared by Hanley & McNeil test. Results We included 125 HD patients with the following characteristics: median age was 67 [53; 78] years; 60% of men; 41% of diabetic and median dialysis vintage of 30 [16; 54] months. Among them, 46% were classified as “Frail” according to Fried. The median follow up was 49 [19; 60] months (Table 1). The ability (AUC) of Fried score, myostatin, IGF-1 and DHEA-S to predict mortality was significant and comparable: 0.72 (95% CI: 0.63 to 0.80), 0.72 (95% CI: 0.64 to 0.80), 0.68 (95% CI: 0.59 to 0.76) and 0.73 (95% CI: 0.64 to 0.80), respectively (Fig. 1). Combining (by logistic regression) one biomarker with Fried score improved significantly the AUC with myostatin (AUC = 0.79, 95% CI: 0.71 to 0.86, p = 0.0049), IGF-1 (AUC = 0.78, 95% CI: 0.70 to 0.85, p = 0.0099) and DHEA-S (AUC = 0.79, 95% CI: 0.71 to 0.86, p = 0.0018) compared to Fried score alone. Compared to biomarker alone, the combination also improved significantly AUC for myostatin and IGF-1 (p = 0.035 and p = 0.011 respectively) but not for DHEA-S. The combination of several biomarkers with Fried score did not significantly improve mortality prediction compared to the combination of a single biomarker with Fried score. Conclusion The study suggests that combining Fried frailty score with either myostatin, IGF-1 or DHEA-S concentration improves the prediction of five-year mortality in chronic HD patients.