Cinobufacini, a compound extracted from bufo toad, is a traditional Chinese medicine(TCM) that has been shown to have efficacy in cancer treatment.The cinobufacini injection is widely used in patients with moderate and advanced liver cancer in China.In the present study, we aimed to determine the effects of cinobufacini injection for this specific category of patients.A search for randomized control trials(RCTs) using cinobufacini was conducted in the PubMed, EMBASE, CENTRAL, and the other four major Chinese databases.The systematic review was performed according to the recommendations of the Cochrane collaboration, and the RevMan 5.3.software was used for statistical analysis.A random-effects model was used to perform the data.Risk ratios(RR) with corresponding 95% confidence interval were calculated according to Cochrane handbook.A total of 11 RCTs consisting of 728 patients were included.All of the trials demonstrated significantly improved total response rates, total response rates of Karnofsky Performance Score(KPS), 1-to 2-year survival rates, and quality of life in the intervention groups injected with cinobufacini.There was no statistically significant difference between the groups(cinobufacini versus no cinobufacini; cinobufacini plus transcatheter arterial chemoembolization(TACE) versus TACE only) in terms of the 6-month survival rate, clinical benefit rate and clinical benefit rate of KPS.This systematic review demonstrated the beneficial effects of cinobufacini injection in terms of total response rate and the 1-to 2-year survival rate in patients with moderate and advanced liver cancer.The efficacy for the cinobufacini injection group might be better than that of the control group for treatment of moderate and advanced liver cancer.Given that the majority of the trials were of low quality, more high-quality prospective RCTs with strict design in accordance with CONSORT for TCM are needed.