Objective To investigate the effect and underlying mechanism of Shizao decoction (SZD) on inducing apoptosis of breast cancer transplanted tumor in nude mice. Methods SKBR3 cells were cultured and transplanted tumor models were constructed in nude mice. The inhibition of tumor growth in mice was observed by continuous intragastric administration for 4 weeks. After the administration, the nude mice were killed and the tissues of transplanted tumor were separated. The lactate dehydrogenase (LDH) kit was uesd to detect LDH produce in transplanted tumor cells of transplanted tumor. The morphological changes in the cells of transplanted tumor tissue were observed by Hoechst33342-PI staining, the reactive oxygen species (ROS) content of the cells was evaluated by DCFH-DA staining, and the mitochondrial membrane potential was evaluated by JC-1 staining. The ELISA test was used to detect Caspase3,Caspase8 and Caspase9 enzyme activity in cells of transplanted tumor. Western blot test was used to detect Fas and FasL protein expression. The qPCR test was used to detect Caspase3, Caspase8, Caspase9, Fas and FasL gene expression. Results Contrasted with the model group, the statistical results showed that the SZD could increase LDH produce cells of transplanted breast cancer in nude mice, could observe the morphological characteristics of typical apoptosis, could rise the ROS content, could emerge the prominent mitochondrial depolarization, could increase the genic expression and the enzymic activity of Caspase3, Caspase8, and Caspase9, and could increase the gene/protein expression of Fas and FasL. Conclusion The SZD can induce apoptosis of transplanted tumor. The apoptotic Caspase pathway and Fas/FasL pathway may be involved in the regulation of apoptosis in tissue of transplantation tumor.