ABSTRACT: BACKGROUND:Interferon gamma (IFN-?) is a key regulatory cytokine, which plays an important role in antiviral defense of an infected host. However, the association between the IFN-? +874T/A gene polymorphism and hepatitis virus-related diseases is heterogeneous. METHODS:Based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, a comprehensive literature search of eligible studies in Embase, Pubmed, and the Cochrane Library was undertaken through November 2014. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to measure the strength of the models. RESULTS:Seventeen case-control articles, including 24 studies with 5503 individuals, met the inclusion criteria. The results indicated a statistically significant association between the IFN-? +874T/A polymorphism and hepatitis virus-related diseases in a recessive gene model (AA vs. TT+TA: OR=1.350, 95% CI=1.101-1.657, P=0.004, I2%=54.3, and PQ=0.001 for heterogeneity), especially in Asians (OR=1.407, 95% CI=1.035-1.911, P=0.029, I2%=61.9, and PQ=0.005 for heterogeneity) and hepatitis B virus (HBV)-related disease (OR=1.486, 95% CI=1.195-1.849, P=0.000, I2%=40.4, and PQ=0.053 for heterogeneity). CONCLUSIONS:The evidence suggests that the IFN-? +874T/A polymorphism increases the risk of hepatitis virus-related diseases, especially in Asians and HBV-related diseases. Further studies on this topic in different ethnicities, especially genome-wide association studies, should be conducted to strengthen our results.