Previous studies have shown that Wnt signaling is involved in postnatal mammalian myogenesis; however, the downstream mechanism of Wnt signaling is not fully understood. This study reports that the murine four-and-a-half LIM domain 1 (Fhl1) could be stimulated by β-catenin or LiCl treatment to induce myogenesis. In contrast, knockdown of the Fhl1 gene expression in C2C12 cells led to reduced myotube formation. We also adopted reporter assays to demonstrate that either β-catenin or LiCl significantly activated the Fhl1 promoter, which contains four putative consensus TCF/LEF binding sites. Mutations of two of these sites caused a significant decrease in promoter activity by luciferase reporter assay. Thus, we suggest that Wnt signaling induces muscle cell differentiation, at least partly, through Fhl1 activation.