PFTK1 was a cell division cycle 2-related serine/threonine protein kinase, which was up-regulated in breast cancer tissues and breast cancer lines. And up-regulated PFTK1 was highly associated with grade, axillary lymph node status, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PFTK1 was related to the poor breast carcinoma patients' overall survival. Here, we first discovered and confirmed that cyclin B was a new interacting protein of PFTK1, and the complex might increase the amount of DVL2, which triggers Wnt/β-catenin signaling pathway. Furthermore, knockdown of PFTK1 attenuated cell proliferation, anchorage-independent cell growth, and cell migration and invasion by inhibiting the transcriptional activation of β-catenin for cyclin D1, MMP9, and HEF1, whereas exogenous expression of PFTK1 might promote MDA-MB-231 cells proliferation, migration, and invasion via promoting PFTK1-DVL2-β-catenin axis. Our findings supported the notion that up-regulated PFTK1 might promote breast cancer progression and metastasis by activating Wnt signaling pathway through the PFTK1-DVL2-β-catenin axis.