Background: To evaluate the chemotherapy toxicity of 5-fluorouracil (5-FU) in the treatment of invasive moles. Methods: We conducted a retrospective study of therapeutic satisfaction, recurrence, and toxicity in 17 patients treated with 5-FU in the Zhuzhou Central Hospital, from 2015 to 2020. Results: After a single-agent 5-FU treatment a complete remission of low-risk invasive moles was observed, and remission of high-risk invasive moles reached rates of 76.5%. After 4–5 chemotherapy cycles, 5-FU reduced serum human chorionic gonadotropin (hCG) to normal levels in invasive moles. Furthermore, a toxicity assessment revealed that 5-FU chemotherapy has low toxicity and is generally acceptable for patients. Conclusions: 5-FU offers high efficacy in both low-risk and high-risk invasive moles, with low chemotherapy toxicity.