Objective To investigate the prevention efficiency of Pegylated recombinant human granulo⁃ cyte stimulating factor（PEG⁃rhG⁃CSF）on chemotherapy⁃naïve osteosarcoma patients treated by pirarubicin and cisplatin. Methods 77 chemotherapy ⁃naïve osteosarcoma patients were enrolled for the study. The patients were non ⁃ randomly divided into a control group（rh ⁃CSF group）with 25 patients and an experiment group（rhG ⁃CSF combined with PEG⁃rhG⁃CSF group）with 52 patients，according to whether they received PEG⁃rhG⁃CSF after AP chemotherapy. The prevention effect of PEG⁃rhG⁃CSF on reduction of neutrophils after chemotherapy were evaluat⁃ ed. Results Prophylaxis of PEG⁃rhG⁃CSF significantly reduced the incidence of Ⅲ⁃Ⅳ degree of ANC reduction， shorten the duration of ANC reduction，decreased the dosage and days of supplemental usage of rhG⁃CSF，reduced the incidence of FN and shorten the days of antibiotic usage（all P < 0.05）. Conclusion Prophylaxis of PEG⁃rhG⁃ CSF can effectively prevent the occurrence and duration of neutropenia with good safety. It is beneficial to ensure the following high⁃dose and high⁃intensity chemotherapy for osteosarcoma patients.