Wnt /β-catenin signaling plays an important role in tumor cell dedifferentiation and proliferation. Wnt proteins are a family of secreted glycoproteins. Abnormal activation of wnt signaling results in tumor progression. Wnt proteins binds to the frizzled receptors and LRP5/6 co-receptors and through the stabilization of β-catenin a critical mediator, initiates a complex signaling cascade that plays an important role in regulating cell proliferation and differentiations. The elevated levels of oncogenic protein-β-catenin have been observed in many of the human cancers, indicating that this pathway plays an important role in tumor development. The wnt signaling can be inhibited at the extracellular level, at regulatory protein level and also by targeting the expressions of β-catenin by protein knockdown and by targeting the downstream mediators of β-catenin signaling such as c-myc, cyclin D1, PPARS and COX-2. In this review we discuss the effects of  NSAIDS and flavanoids that are being used or explored to target the β-catenin signaling in the treatment of cancers.