To study the possibility of oral gene therapy using live attenuated Salmonella. A live attenuated AraA^- autotrophic mutant of Salmonella typhimurium (SL3261) was used as carrier for eukaryotic expression vectors EGFPN1, pCMVmIL-12, pCMVmGM-CSF and was administered orally to BALB/c and C57BL/6 mice. After 6 weeks, these mice were challenged with 4T₁ or Lewis tumor cells respectively. Flow cytometer and laser scanning confocal microscopy were used to detect the expression of GFP in murine tissues. PCR and ELISA were used to detect the integration and expression of mIL-12, mGM-CSF gene. The survival time of mice was also investigated. GFP expression and mIL-12, mGM-CSF gene integration could be detected in murine liver, spleen, intestine, kidney and tumor. The serum level of mIFN-γ，mIL-12 increased significantly in the mIL-12 orally treated mice (P＜0.05); The serum level of mGM-CSF increased also in mGM-CSF orally treated mice (P＜0.05); which resulted in the prolongation of the survival time of those mice, compared with the control (P＜0.05). Oral gene therapy using live attenuated Salmonella has the potential to be a simple, effective and above all, safe way against tumor.