B-cell CLL/lymphoma 9 (BCL9) is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types, mainly through potentiating the Wnt/β-catenin signaling. However, increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles. Herein, we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular, physiological, or pathological processes. Moreover, we also concluded that the targeted inhibitors disrupt the interaction of β-catenin with BCL9 reported recently.