The association of VEGF+405G/C (where VEGF is vascular endothelial growth factor) polymorphism and malignancy susceptibility attracts considerable attention because VEGF is one of the most potent angiogenic factors and plays a critical role in the onset and development of malignancy. However, the published findings remain inconclusive. In order to derive a more precise assessment of the association, we performed a meta-analysis including 30 published case-control studies from PubMed, Embase, and Ovid databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. In the pooled analyses, no significant association was found between VEGF+405G/C polymorphism and malignancy susceptibility in different genetic models (G-allele vs. C-allele: OR = 1.00, 95% CI: 0.93–1.07; CC vs. GG: OR = 1.01, 95% CI: 0.88–1.15; GC+CC vs. GG: OR = 1.00, 95% CI: 0.91–1.10; CC vs. GC+GG: OR = 1.01, 95% CI: 0.90–1.13). When stratified by ethnicity, a weak association between this polymorphism and malignancy susceptibility was found in African under allelic frequency comparison (OR = 0.65, 95% CI: 0.43–0.98) and dominant genetic model comparison (OR = 1.95, 95% CI: 1.09–3.50). In summary, although our meta-analysis indicated a weak association of VEGF+405G/C polymorphism with malignancy susceptibility in African, no persuasive evidence of association between the polymorphism and malignancy susceptibility was detected in the pooled analyses. Therefore, more studies with larger scale of participants, especially Africans, are required to further evaluate gene-environment interaction on this polymorphism and malignancy susceptibility.