To assess the efficacy and safety of Xiyanping injection for hand foot mouth disease. All Clinical studies of Xiyanping injection for hand foot mouth disease were searched from Cochrane library, Medline, EMbase, CBM, CNKI, Wanfang and VIP. Selection of trials for inclusion, data extraction, assessment of methodological quality were completed by two independent screening. The quality of the included documents was evaluated by the Cochrane collaboration's tool for assessing risk of bias and allocation concealment. Revman 5. 1 software was used for data analysis. Twenty-four randomized controlled trials were included (involving 2 974 patients), in which, only one study was true RCT and two studies used incorrect methodology. The remaining studies did not provide allocation concealment, blind or loss-up information. The results of Meta-analysis were presented below. Compared with conventional treatment measures, the efficiency of Xinyanping injection group was better (OR = 4.26, 95% Cl [3.19, 5.69]). Both fever clearance time (WMD = - 1.48, 95% Cl [- 1.85, - 1.11]) and skin eruption eliminating time (WMD = - 1.78, 95% Cl [- 2.84, - 0.72]) of Xinyanping injection group were shorter than the control group. Researches with ADR/AE information of Xinyanping injection showed that the symptoms of ADR/AE were slight. The systematic review suggests that Xiyanping injection in the combination with conventional treatment may improve the efficacy of the treatment of hand foot mouth disease. However, as all of the included trials were published in Chinese and of poor quality, we cannot draw a sure conclusion. More rigorous trials with high quality are required.