Cancer cachexia is a complex syndrome involved in muscle wasting, fat depletion, fatigue, reduced appetite, and unintentional weight loss. Recent studies have suggested that natural products can prevent cancer cachexia; however, there have been no studies on the effects of Litsea japonica fruit extract on cancer cachexia. This study aimed to identify compounds of L. japonica fruit extracted from water (LJFE-W) and those extracted from 30% ethanol (LJFE-E) for cancer cachexia treatment. In vitro and in vivo models were used for C26 conditioned medium (CM)-induced C2C12 myotubes and C26 tumor-bearing mice. We demonstrated that LJFE-W and LJFE-E regulated myostatin (MSTN), E3 ligase muscle-specific RING finger protein-1 (MuRF1), and muscular atrophy fbox-1 protein (MAFbx32) expression in a CM-induced in vitro model. LJFE-E ameliorated conditioned medium-induced myotube atrophy in cultured C2C12 myotubes. In contrast, LJFE-W and LJFE-E stimulated the Akt-mTOR signaling pathway for protein synthesis in C2C12 myotubes. In animal models, the LJFE-E-injected C26 tumor-bearing group showed lower transcript-level expression of MSTN, MuRF1, and MAFbx32 in the gastrocnemius muscles than the C26 tumor-bearing group. LJFE ameliorated muscle atrophy in the cancer cachexia model by inhibiting MSTN. Thus, LJFE can be used as a supplement to cancer cachexia therapy.