Abstract: Objective: To compare the clinical efficacy and toxicity of raltitrexed or fluorouracil plus gemcitabine in the treatment of patients with advanced breast cancer. Methods: The curative effects and adverse reactions in 57 cases of advanced breast cancer treated by different therapies were analyzedretrospectively. Group A( 31 cases) were administered raltitrexed plus gemcitabine and group B( 26 cases) fluorouracil plus gemcitabine. Group A were given raltitrexed 3 mg /m2at day 1， and gemcitabine 1 000 mg /m2 at day 1 and day 8; group B were administered fluorouracil 500 mg /m2 from day 1 to day 5，and gemcitabine 1 000 mg /m2 at day 1 and day 8. The therapies were repeated every 21 days for two cycles. Results: The response rates of group A and group B were 38. 71% and 30. 77%， respectively. The difference was not significant between the two groups ( P ＞ 0. 05) . The difference in the occurrence of anorexia，vomiting，diarrhea and transaminase elevation had statistical significance between the two groups( P ＜ 0. 05 to P ＜ 0. 01) ，and the difference in leukopenia was not obvious( P ＞ 0. 05) . Conclusions: The therapy of raltitrexed plus gemcitabine is effective and has sight adverse reactions in treatment of advanced breast cancer， it can be used as one of the regimens for patients with advanced breast cancer.