Kindlin-2, as a focal adhesion protein, controls integrin activation. However, the association of Kindlin-2 with cancer-related signaling pathways is unknown. Here, we identified a novel direct interaction between Kindlin-2 and the active β-catenin. Importantly, Kindlin-2 forms a tripartite complex with β-catenin and TCF4. Mechanistically, Kindlin-2 selectively strengthens the occupancy of β-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the β-catenin–Axin2–Snail cascade is required for Kindlin-2-induced tumor cell invasion. Our data reveal that Kindlin-2 is a new regulator of Wnt signaling, providing a mechanistic insight into the role of Kindlin-2 in cancer progression.