Objective To observe the therapeutic effect of attenuated Salmonella carrying siRNA-STAT3 plasmid on transplanted prostate cancer in mice, and investigate the mechanism of siRNA-STAT3 inducing apoptosis of prostate cancer cells in mice. Methods The transplanted prostate cancer models of mice were built, and then the mice were randomly divided into Mock group, pGC-Si-Scramble group and pGC-Si-STAT3 group. The general status of the mice was observed and the changes of tumor volume were recorded. The expression levels of mRNA and protein of STAT3 and its downstream genes such as Bcl-2, c-Myc, HIF-1, cyclinD1 were analyzed with RT-PCR and western blotting, and the apoptosis of tumor cells was detected with flow cytometry. Results Compared with the Mock group, the tumor weight and tumor volume in pGC-Si-STAT3 group were significantly decreased (P<0.05). The result of flow cytometry revealed that the early apoptotic rate of tumor cells in pGC-Si-STAT3 group was (29.1±1.6)%, which was significantly higher than that of pGC-Si-Scramble group (14.7±1.4)% and Mock group (8.9±1.8)% (P<0.05). The mRNA expression levels of STAT3 and its downstream genes Bcl-2 and c-Myc in the pGC-Si-STAT3 group were significantly decreased (P<0.05), and the protein expression levels of STAT3 and its downstream genes HIF-1 and cyclinD1 were also decreased (P<0.05), compared with the Mock group. Conclusion The attenuated Salmonella carrying siRNA-STAT3 plasmid could inhibit the growth of transplanted prostate cancer in mice by regulating the expressions of STAT3’s downstream genes and inducing the apoptosis of tumor cells.