Objective: Insulin-like growth factor-1 (IGF-1) and inflammation have both been linked to high cardiovascular risk and mortality in the general population, as well as in hemodialysis (HD) patients. We hypothesized that the association of low IGF-1 with chronic inflammation may increase the mortality risk in HD patients. Design: We investigated the interactions between inflammatory biomarkers (IL-6 and TNF-α) and IGF-1 as predictors of death over a 4. years of follow-up (median - 47. months, interquartile range - 17.5-75. months) in 96 prevalent HD patients (35% women, mean age of 64.9 ± 11.6. years). Results: A significant interaction effect of low IGF-1 (defined as a level less than median) and high IL-6 (defined as a level higher than median) on all-cause and cardiovascular mortality was found: crude Cox hazard ratios (HR) for the product termed IGF-1 × IL-6 were 4.27, with a 95% confidence interval (CI): 2.10 to 8.68 (P < 0.001) and 7.49, with a 95% CI: 2.40-24.1 (P = 0.001), respectively. Across the four IGF-1-IL-6 categories, the group with low IGF-1 and high IL-6 exhibited the worse outcome in both all-cause and cardiovascular mortality (multivariable adjusted hazard ratios were 4.92, 95% CI 1.86 to 13.03, and 14.34, 95% CI 1.49 to 137.8, respectively). The main clinical characteristics of patients in the low-IGF-1-high IL-6 group didn't differ from other IGF-1-IL-6 categorized groups besides gender that consequently was inserted in all multivariable models together with the other potential confounders. Conclusions: An increase in mortality risk was observed in HD patients with low IGF-1 and high IL-6 levels, especially cardiovascular causes.