Objective To investigate the clinical effect and toxicity of TC chemotherapy combined with radiotherapy in treatment of high-risk endometrial cancer after surgery. Methods Patients (82 cases) with high-risk endometrial cancer after surgery who came to the Fourth People's Hospital of Wuxi City from February 2008 to February 2009 were randomly divided into control (41 cases) and treatment (41 cases) groups. The patients in the control group were given radiotherapy after surgery, while the patients in the treatment group were given TC chemotherapy combined with radiotherapy. The rates of tumor recurrence and survival in the two groups were calculated, and the toxic effects of drugs were observed. Results The recurrence rate of vagina and pelvic, and the distant metastasis rate of retroperitoneal lymph nodes and lung in treatment group were significantly lower than those in the control group, with significant difference between two groups (P < 0.05). Five year survival rate of the treatment group was higher than that of control group, with significant difference between two groups (P < 0.05). Toxicity reaction such as skin reaction, gastrointestinal reaction (included nausea, vomiting, diarrhea), bone marrow suppression, neurotoxicity, and urinary tract reaction happened in two groups during the course of treatment. The rate of bone marrow inhibition in the treatment group was higher than that in the control group, with significant difference between two groups (P < 0.05). Conclusion TC chemotherapy combined with radiotherapy is an effective treatment for high-risk endometrial cancer after surgery, and the local recurrence rate, distant metastasis, and five year survival rate are significantly better than pure radiotherapy. But the combination treatment has the disadvantage of bone marrow suppression, the blood cell levels of the patients needs to be paid close attention, and hematopoietic factor should be complementally used when necessary.