Since the discovery of the first mammalian Wnt proto-oncogene in virus-induced mouse mammary tumors almost four decades ago, Wnt signaling pathway and its involvement in cancers have been extensively investigated. Activation of this evolutionarily conserved pathway promotes cancer development via diverse mechanisms. Cancer is a complex disease and one outstanding conceptual framework for understanding its biology is the “Hallmarks of Cancer”. In this review, we focus on the involvement of Wnt signaling in the ten hallmarks of human cancer. These widespread roles of Wnt signaling in human cancers highlight the importance and feasibility of targeting this signaling pathway for cancer treatment.