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Background: The results of different studies have indicated the possible associations of TLR4 and IL-8 genes polymorphisms with Age-related Macular Degeneration (AMD). A meta-analysis study was designed to evaluate the possible associations of TLR4 (rs4986790/c.896A>G and rs4986791/ c.1196 C > T) and IL-8 (rs4073/c.251A>T and rs2227306/c.781 C > T) genes polymorphisms with AMD., Method: A systematic literature search was carried out in PubMed, Embase, Web of Science, and Scopus databases to identify relevant publications. Pooled Odds Ratio (OR) with 95% Confidence Interval (CI) was used to evaluate the power of association., Results: A total of 12 case-control studies with 4804 AMD patients and 4422 healthy controls were included in this meta-analysis. The analysis of genotypic and allelic models demonstrated significant associations between IL-8 c.781 C > T (CC vs. TT+TC: OR = 0.62 [0.48-0.81], P < .01; CC vs. TC: OR = 0.65 [0.48-0.89], P < .01; TT vs. CC: OR = 1.64 [1.04-2.57], P = .03; and C vs. T: OR = 0.71 [0.65-0.79], P < .01) and risk of AMD, which all of them passed Bonferroni correction for multiple testing ( P -value≤0.01), except for TT vs. CC model. In addition, we found associations under the genotypic model of TLR4 c.896A>G (AA vs. AG+GG: OR = 0.73 [0.55-0.97], P = .03; and AA vs. AG: OR = 0.71 [0.53-0.95], P = .02) although after Bonferroni correction ( P '-value<0.02) none of these associations remained significant. However, the data from this meta-analysis declined the associations of TLR4 c.1196 C > T and IL-8 c.251A>T polymorphisms with AMD., Conclusion: The current meta-analysis study suggested that IL-8 c.781 C > T polymorphism is associated with susceptibility to AMD.