Muscle atrophy is a prognostic factor for patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Liver Frailty Index (LFI) is a simple physical function test; however, an association between LFI and muscle mass remains unclear. We aimed to investigate utility of LFI for predicting muscle atrophy in CLD patients with HCC. We enrolled 138 CLD patients with HCC (77 years, female/male 34.8%/65.2%). Muscle mass was assessed by skeletal muscle index and patients were classified in to Muscle atrophy group (n=109) or Non-muscle atrophy group (n=29). Physical frailty was assessed by LFI. The optimal cut-off value of LFI for predicting muscle atrophy was identified by receiver operating characteristic (ROC) analysis. In the Muscle atrophy group, the prevalence of pre-frail/frail was significantly higher than the Non-muscle atrophy group (87.2% vs. 58.6%, P=0.0005). In the logistic regression analysis, female and pre-frail/frail were identified as independent factors associated with muscle atrophy (pre-frail/frail; OR 3.601, 95%CI 1.381-9.400, P=0.0088). In patients with normal grip strength, 71.1% of patients were pre-frail/frail, in which 82.8% of patients showed muscle atrophy. ROC statistics provided an AUC of 0.74 and an LFI cut-off value of 2.94 for predicting muscle atrophy (sensitivity 88.06%, specificity 52.17%, accuracy 77.91%). We demonstrated that pre-frail/frail was an independent factor for muscle atrophy in CLD patients with HCC. Furthermore, LFI predicted muscle atrophy with high sensitivity even in patients with normal grip strength. Thus, LFI may be useful screening tool for muscle atrophy in CLD patients with HCC. This article is protected by copyright. All rights reserved.