This study was designed to evaluate the synergistic cytotoxicity of herb prescription, Palgin, in adriamycin-treated cancer cells. The combination of Palgin and adriamycin synergistically augmented the cytotoxicity of Chang and HL-60 cells, but not in Hep3B and Alexander cells. The cytotoxicity of two drugs was revealed as apoptosis characterized by nuclear fragmentation. The apoptotic cell death was accompanied by the activation of caspase-3 as well as cleavage of poly(ADP) ribose polymerase (PARP) in Chang cells. Interestingly, a synergistic increase in apoptosis by the combination of two drugs was accompanied by the enhancement of Fas and Fas ligand (FasL) expression in Chang cells. Taken together, the combination of Palgin and adriamycin significantly augmented the apoptotic cytotoxicity of Fas-positive cells, such as Chang and HL-60 cells, via activation of caspase signaling pathway. This notion will provide a new trial to treat cancer patients in clinical fields as a complementary treatment of Western and Oriental medicine.