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Abstract Background To evaluate the effectiveness and safety of HuoXueHuaYu (HXHY) therapy in treating nonalcoholic fatty liver disease (NAFLD) through a systematic review and meta-analysis. Methods We performed comprehensive searches on Embase, Pubmed, Cochrane Library, CNKI, VIP and Wanfang databases up to June 2017 for randomized controlled trials using HXHY in the treatment of NAFLD compared with conventional treatment. Results This meta-analysis included 13 studies involving 1429 patients which 775 patients belonged to HXHY group and 654 patients belonged to conventional treatment group. The results of meta-analysis showed that HXHY can significantly improve B ultrasonic level (OR = 2.33; 95% CI:1.60, 3.40; P < 0.00001) of NAFLD compared with conventional treatment. As to lipids, HXHY was tested to be better on reduction of total cholesterol (TC) (MD = -0.38, 95% CI: − 0.48, − 0.29; P < 0.00001) and triglyceride (TG) (MD = -0.31; 95% CI: − 0.37, − 0.24; P < 0.00001) than conventional treatment. HXHY also had a greater beneficial effect on liver function in reducing alanine transaminase (ALT) (MD = -1.69; 95% CI: − 2.24, − 1.14; P < 0.00001) and aspartate transaminase (AST) (MD = -22.53; 95% CI: − 33.16, − 11.90; P < 0.00001) compared with conventional treatment. HXHY can also significantly improve the effective rate (OR = 3.55; 95% CI:2.65, 4.76; P < 0.00001) compared with conventional treatment. No serious adverse reactions were reported. Conclusions HXHY seems to be an effective and safe therapy for NAFLD. It is suggested that further study of HXHY in the treatment of NAFLD requires trials with rigorous design, multicenter, large-scale and high-quality worldwide.