Kindlin 2, as an integrin-associated protein, is required for myocyte elongation and fusion. However, the association of Kindlin 2 with muscle differentiation-related signaling pathways is unknown. Here, we identified a mechanism that Kindlin 2 regulates myogenic regulatory factors myogenin via a canonical Wnt/β-catenin signaling. We found that knockdown of Kindlin 2 leads to the abolishment of β-catenin/TCF4-mediated transcription in C2C12 cells, followed by the impairment of myogenic differentiation. Mechanistically, nuclear translocation of both Kindlin 2 and β-catenin is induced during myogenic differentiation. In particular, Kindlin 2 forms a tripartite complex with active β-catenin and TCF4, and hence co-occupied on the promoter of myogenin to enhance its expression. Functionally, depletion of Kindlin 2 impairs myogenic differentiation via downregulation of myogenin. Taken together, our data reveal that Kindlin 2 is required for Wnt signaling-regulated myogenic differentiation, providing a mechanistic insight into the role of Kindlin-2 in muscle development.