The tumor necrosis factor-α (TNF-α)-308G/A gene polymorphism influences the pathogenesis and evolution of HIV-1 disease. Many studies have evaluated the association between this polymorphism and HIV-1 susceptibility, but the exact relationship between them remains ambiguous and contradictory. Accordingly, the present study evaluates the exact association between TNF-α-308G/A gene polymorphism and HIV-1 susceptibility. A systematic literature search was conducted and the case-control studies that were found assessing the association between TNF-α-308G/A gene polymorphism and HIV-1 susceptibility were analyzed. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by a fixed effect model. Heterogeneity was analyzed by Cochran's Q and the I(2) statistics. Publication bias was assessed using the Begg's funnel plot and Egger's test. A total of 679 cases and 873 controls from five studies were included. Overall, no significant relationship was found between TNF-α-308G/A gene polymorphism and HIV-1 susceptibility in this meta-analysis study (A versus G genotype model: OR=0.89, 95% CI=0.59-1.32, p=0.553; GG versus AA+AG model: OR=1.23, 95% CI=0.75-2.02, p=0.407; GG+AG versus AA model: OR=1.40, 95% CI=0.70-2.82, p=0.345; GG versus AA model: OR=1.39, 95% CI=0.69-2.80, p=0.362; AG versus AA model: OR=1.43, 95% CI=0.70-2.96, p=0.329; GG+AA versus AG model: OR=0.76, 95% CI=0.44-1.29, p=0.304). The meta-analysis found no marked association between TNF-α-308G/A gene polymorphism and HIV-1 susceptibility.