Irradiation from diverse sources is ubiquitous and closely associated with human activities. Radiation therapy (RT), an important component of multiple radiation origins, is a common therapeutic modality for cancer. More importantly, RT provides significant contribution to oncotherapy by killing tumor cells. However, during the course of therapy, irradiation of normal tissues can result in a wide range of side effects, including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Although numerous promising radioprotective agents have emerged, only a few have successfully entered the market because of various limitations. At present, the widely accepted hypothesis for protection against radiation-caused injury involves the Wnt canonical pathway. Activating the Wnt/β-catenin signaling pathway may protect the salivary gland, oral mucosa, and gastrointestinal epithelium from radiation damage. The underlying mechanisms include inhibiting apoptosis and preserving normal tissue functions. However, aberrant Wnt signaling underlies a wide range of pathologies in humans, and its various components contribute to cancer. Moreover, studies have suggested that Wnt/ β-catenin signaling may lead to radioresistance of cancer stem cell. These facts markedly complicate any definition of the exact function of the Wnt pathway. Irradiation from diverse sources is ubiquitous and closely associated with human activities. Radiation therapy (RT), an important component of multiple radiation origins, is a common component of multiple radiation origins, is a common component of therapeutic modality for cancer. More importantly, RT provides significant contributions to oncotherapy by killing tumor cells. However, , during the course of therapy, irradiation of normal tissues can result in a wide range of side effects, including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. entered the market because of various limitations. At present, the widely accepted hypothesis for protection against radiation-caused injury involves the Wnt canonical pathway. Activating the Wnt / β-catenin signaling pathway may protect the salivary gland, oral mucosa, and gastrointestinal epithelium from radiation damage. The underlying mechanisms include inhibiting apoptosis and preser However, aberrant Wnt signaling underlies a wide range of pathologies in humans, and its various components contribute to cancer. Moreover, studies have suggested that Wnt / β-catenin signaling may lead to radioresistance of cancer stem cells. These facts markedly complicate any definition of the exact function of the Wnt pathway.