The development of glioma is a complex process which may be influenced by many factors including the epidermal growth factor (EGF) gene polymorphism. Previous studies showed that EGF rs4444903 polymorphism could result in increased risk of tumorigenesis in multiple human cancers, but published data regarding the association between EGF rs4444903 polymorphism and glioma risk were inconsistent. To derive a more precise estimation of the association between EGF rs4444903 polymorphism and glioma risk, we performed a systematic review and meta-analysis of previous published studies. PubMed, Embase, and the Wanfang databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to assess the strength of the association. Ten published studies with 1,891 glioma cases and 2,836 controls were finally included into the study. Overall, there was a significant association between EGF rs4444903 polymorphism and glioma risk in all four genetic models (the allele model: OR=1.25, 95 % CI 1.15-1.37, P<0.001; the codominant model: OR=1.65, 95 % CI 1.36-1.99, P<0.001; the dominant model: OR=1.27, 95 % CI 1.12-1.44, P<0.001; the recessive model: OR=1.48, 95 % CI 1.25-1.75, P<0.001). Subgroup analyses by ethnicity showed that EGF rs4444903 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In conclusion, the results suggest that there is a significant association between EGF rs4444903 polymorphism and glioma risk, and genotypes of EGF rs4444903 mutation contribute to increased host susceptibility to glioma.