Objective To evaluate the efficacy and safety of percutaneous vertebroplasty (PVP) combined with sustained-release fluorouracil for the treatment of vertebral metastasis tumor. Methods A total of 72 cases with vertebral metastasis tumor were enrolled in the study. Thirty-seven cases underwent percutaneous vertebroplasty combined with sustained -release fluorouracil, 35 underwent percutaneous vertebroplasty alone. Efficacy and safety were evaluated through clinical symptoms, survival analysis and radiology. Results Local tumor control and pain relief were achieved in 67.6% (25/37) and 89.2% (33/37) of the patients treated by percutaneous vertebroplasty combined with sustained-release fluorouracil combined, in 42.9% (15/35) and 85.7% (30/35) of those treated with percutaneous vertebroplasty alone. Significant difference was found between two groups for the local tumor control rate (P=0.035), but not for the quality of life, pain relief and survival (P=0.124, 0.462, 0.498, respectively). Conclusions The new treatment using percutaneous vertebroplasty combined with sustained-release fluorouracil for vertebral metastases is safe and effective, which substantially relieves the severe pain in patient with advanced vertebral invasion, and also improves the quality of life and oncological control.