〔Abstract〕 Objective To explore the effects of Vascular Endothelial Growth Factor A (VEGFA)rs2010963 and rs3025039 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors. Methods A total of 104 pediatric patients with brain tumors receiving standardized chemotherapy were enrolled. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for VEGFA rs2010963 and rs3025039 genotyping. The χ² test was applied to analyze the association between genotypes and chemotherapy_related toxicities.Cox proportional hazards regression was used to evaluate the correlations of clinicopathological characteristics and genotypes with the progression_free survival (PFS). In addition, bioinformatic analyses were conducted to investigate the regulatory factors potentially affected by the two SNP loci. Results The VEGFA expression in brain tumors (5.17±1.81) was significantly higher than that in normal tissues (4.33±1.56, P<0.001). Patients with high VEGFA expression had significantly worse overall survival than patients with low VEGFA expression (P<0.001). Among the 104 children with brain tumors included, the rs2010963 CC, CG, and GG genotypes accounted for 14.42%, 55.77%, and 29.81%, respectively. The frequencies of C and G alleles were 42.31% and 57.69%, respectively. The rs3025039 CC, CT, and TT genotypes accounted for 70.19%, 25.96%, and 3.85%, respectively. The frequencies of C and T alleles were 83.17% and 16.83%, respectively. The children with the rs3025039 CC genotype had significantly higher incidences of thrombocytopenia (46.58%) and gastrointestinal toxicity (56.16%), and significantly lower incidences of coagulation disorders (4.11%) than CT genotype carriers (22.22%, 33.33%, and 50.00%, respectively, P<0.05). They had significantly lower incidences of dyslipidemia (2.74%) than TT genotype carriers (14.82%, P<0.05). The tumor type and the rs2010963 genotype were significantly associated with PFS (P<0.05) in univariable and multivariable Cox regression analysis. Bioinformatic analysis indicated that the rs2010963 and rs3025039 polymorphisms regulated VEGFA expression by affecting the binding of transcription factors and miRNAs to their target gene sequences, respectively. Conclusion The VEGFA rs3025039 CC genotype significantly affects the risk of thrombocytopenia, gastrointestinal toxicity, coagulation disorders, and hyperlipidemia, while the rs2010963 CG genotype significantly affects the risk of brain tumor progression.