Mucoepidermoid carcinoma (MEC) is the most common primary malignancy in the salivary glands; however, its oncogenesis is poorly understood. Here, we show that the homo sapiens basic leucine zipper and W2 domains 1 (BZW1 or BZAP45) is a critical factor in the regulation of MEC growth. Firstly, BZW1 was highly expressed in MEC tissues and cells, determined by quantitative real time polymerase chain reaction. Higher levels of BZW1 proteins were detected in MEC tissues, particularly in high-grade MEC, by immunohistochemistry. Furthermore, down-regulation of BZW1 expression by infection with BZW1-specific RNAi-expressing lentivirus inhibited Mc3 cell proliferation and colony formation in vitro. In addition, down-regulation of BZW1 expression arrested Mc3 cell cycling at the G(0)/G(1) phase and mitigated Mc3 cell migration and invasiveness in vitro, determined by wound healing and transwell invasion assays. Importantly, down-regulation of BZW1 expression significantly reduced the tumorigenicity of Mc3 cells in vivo, evidenced by the slow progression of small tumors induced by BZW1-specific RNAi expressing Mc3 cells. Apparently, BZW1 is a novel factor, promoting the growth of MEC cells. Our findings may provide a base for design of new strategy for diagnosis and therapy for human MEC.