In this study, we discovered anti-DKK1 antibodies using synthetic libraries and machine learning methods and found that the antibodies binding to DKK1 CRD2 were capable of restoring the Wnt canonical pathway, whereas antibodies binding to DKK1 CRD1 could regulate Wnt non-canonical signaling, promote the immune cell response in vitro, and suppress prostate tumor growth in vivo. This evidence concerns the gene DKK1 and prostate neoplasm.