Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a β-catenin inhibitor and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a β-catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a β-catenin inhibitor, such as a β-catenin nucleic acid inhibitor molecule.