Objective To investigate the effect and underlying mechanism of Shizao decoction ( SZD) on inducing apoptosis in breast cancer transplants in nude mice. Methods SKBR3 cells were cultured and transplanted into nude mice to construct tumor models. SZD was applied by continuous intragastric administration for 4 weeks and its effects on tumor growth were observed. After administration, the mice were killed and the transplanted tumor tissues were separated. Lactate dehydrogenase ( LDH) levels in tumor tissues were detected using an LDH kit. Morphological changes in transplanted tumor tissues were observed by Hoechst33342-propidium iodide staining,reactive oxygen species ( ROS ) were evaluated by 2 ’, 7 ’-dichlorodihydrofluorescein diacetate staining, and mitochondrial membrane potential was evaluated by JC-1 assay. Caspase3, Caspase8, and Caspase9 activities in the transplanted tumor cells were detected by enzyme-linked immunosorbent assay. Fas and Fas ligand ( FasL) protein expression were detected by Western blot. Caspase3, Caspase8, Caspase9, Fas, and FasL gene expression were detected by quantitative polymerase chain reaction. Results Compared with the model group, SZD significantly increased LDH production (P<0. 05, P<0. 01) by transplanted breast cancer cells in nude mice, induced apoptosis,increased the ROS content (P<0. 05) and mitochondrial depolarization ( P<0. 05, P<0. 01), increased the gene expression and enzyme activities of Caspase3, Caspase8, and Caspase9 (P<0. 05, P<0. 01), and increased the gene /protein expression of Fas and FasL (P<0. 05, P<0. 01). Conclusions SZD can induce apoptosis in transplanted breast tumors, possibly via the apoptotic caspase and Fas/ FasL pathways tumor.