Background: Solid tumors represent approximately 90% of adult cancers that threaten public health. People with solid tumors face challenges during their treatment. Granulocyte colony-stimulating factor (G-CSF) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were associated with statistically significantly reduced the risk of neutropenia during treatment, but the effects on overall survival and freedom from treatment failure is still unknown. Objectives: To evaluate the effectiveness of granulopoiesis-stimulating factors prophylaxis to improve survival and prevent adverse effects in the treatment of solid tumors. Methods: Databases including Medline, Cochrane Library, Embase, and ongoing trial websites were systematically searched to identify randomized controlled trials investigating the effects of G-CSF or GM-CSF prophylaxis versus placebo/no prophylaxis for solid tumors. We also checked reference lists of all included studies and any relevant systematic reviews. Included studies were rated by Cochrane Risk of bias tool. Two reviewers independently screened the titles and abstracts for inclusion, extracted data, and evaluated the risk of bias, and disagreements were resolved by the third reviewer. We used the GRADE approach to assess the overall certainty of the evidence. Results: The protocol of this research has been published. This study is ongoing, and will be finished at the end of August, 2024. Conclusion: Findings of this study will present evidence on the efficacy of granulopoiesis-stimulating factors prophylaxis, so as to provide reference for clinical decision-making.