Radiotherapy and chemotherapy are the main therapeutic approaches for patients with malignant tumours, especially advanced tumours. However, they can cause adverse effects, one of which is gastrointestinal mucosal damage, which can greatly affect patients' quality of life. Until now, there have been no effective therapies to avoid or treat these adverse effects. In this study, we used attenuated Salmonella typhimurium (S. typhimurium) to deliver the hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF) to murine gastrointestinal mucosa. We found that attenuated S. typhimurium carrying the HGF or KGF genes can effectively reduce the ratio of tumour to non-tumour carcass weight, repair damage to the gastrointestinal mucosal from chemotherapy, improve the immune response, and reduce the mortality rate of mice. Oral administration of attenuated S. typhimurium with HGF and KGF may be promising as a way of improving the quality of life of patients undergoing radiotherapy and chemotherapy.