HIV-HCV co-infected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, non-alcoholic steatohepatitis (NASH), a known risk factor for mortality. The fatty liver index (FLI), a non-invasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV co-infected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French ANRS CO13 HEPAVIH cohort (983 patients; 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality.After multiple adjustment, individuals with FLI≥60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval]: 1.91 [1.17-3.12], p = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], p=0.004), advanced fibrosis (1.77 [1.00-3.14], p=0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], p<10 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], p=0.015), and HIV CDC clinical stage C (2.88 [1.74-4.79], p<10 ).An elevated fatty liver index (FLI≥60) is a risk factor for all-cause mortality in HIV-HCV co-infected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of non-invasive steatosis biomarkers to help identify co-infected patients with higher mortality risk. This article is protected by copyright. All rights reserved.