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Cisplatin is a well-known platinum-containing anti-cancer drug against bladder, ovarian, lung and testicular cancer. However, the potential effects and molecular targets of cisplatin in human mucoepidermoid carcinoma (MEC) are not fully understood. Here, we investigated the apoptotic effect and underlying mechanism of cisplatin in human MEC cells. The potential effects of cisplatin were evaluated by trypan blue exclusion assay, Western blotting, 4’-6-diamidino-2-phenylindole (DAPI) staining, live/dead assay and immunocytochemistry. Cisplatin suppressed cell growth and enhanced expression of cleaved PAPR in MC3 and YD15 cells. Cisplatin caused morphological change of nuclei and increased the number of ethidium homodimer-1-stained cells. In addition, cisplatin commonly increased Bax activation in both cells, while other Bcl-2 family proteins were not affected. These results suggest that cisplatin might induce apoptosis by activating Bax protein, which would provide baseline data for development of effective treatment strategy against MEC.