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Background Perforin (PRF1) gene mutation can cause the onset of hemophagocytic lymphohistiocytosis (HLH).It has reported that PRF1 Ala91Val polymorphism was related with HLH risk.In the meta-analysis,we aim to evaluate the asso?ciation between PRF1 Ala91Val polymorphism and HLH risk.Methods We accomplished a meta-analysis of six published case-control studies including 391 patients with HLH and 975 controls.We evaluated the quality of each study through Newcastle-Ottawa Scale (NOS).Data analysis was performed with Stata software.Results In general,all studies were of high quality (NOS score higher than 7).There were statistically significant between the PRF1 Ala91Val polymorphism and HLH risk though the pooled analysis [for Ala/Val vs.Ala/Ala:pooled odds ratio(OR) = 3.22,95％ confidence interval (CI) 1.08-9.56,P=0.035,random model;for Ala/Val +Val/Val vs.Ala/Ala:pooled OR=2.96,95％ CI 1.14-7.69,P=0.025,random model].Furthermore,sensitivity analysis also revealed a relationship between PRF1 Ala91Val polymorphism and HLH risk (for Ala/Val vs.Ala/Ala:pooled OR = 5.236,95％ CI 2.72-10.08,P ＜ 0.000,I2=12.1％,Pheterogeneity = 0.332;for Ala/Val + Val/Val vs.Ala/Ala,pooled OR = 4.856,95％ CI 2.66-8.85,P ＜0.000,I2 = 5.9％,Pheterogeneity = 0.373).Funnel plot and Egger's test did not indicate obvious published bias (P = 0.841 for Ala/Val vs.Ala/Ala;P=0.284 for Ala/Val+Val/Val vs.Ala/Ala).Conclusion This meta-analysis indicated that PRF1 Ala91Val polymorphism affects the factor for developing HLH and future studies of PRF1 Ala91 Val on the onset of HLH will be guaranteed.