Adverse event reports related hepatoprotective drugs are increasing. This has important public health implications. Our study aims to investigate the safety of hepatoprotective drugs by combining safety reports with drug utilization data from 2012 to 2014. Utilization data were retrieved from the hospital drug information network of Yangtze River basin and expressed as defined daily doses per 10 000 inhabitants per day. Safety data were collected from the Hubei Adverse Event Reporting System and analysed according to patients' sex, age, occurrence time, route of administration, involved organs or systems, and so on. The relationship between utilization and adverse drug events was used to evaluate the safety of hepatoprotectives by graphical analysis with histogram plots. For the utilization, both consumption sum and dose per inhabitants per day increased from 2012 to 2014. Of the 21 hepatoprotectives, 52.38% were chemical drugs, which accounted for 78.95% of total expenditure and 51.64% of total dose per inhabitants per day. The top three hepatoprotectives were glycyrrhizin, hepatocyte growth-promoting factors, and marine. For the safety, chemical drugs were responsible for 673/916 adverse drug events (73.47%). The gastrointestinal system was most frequently damaged (331, 29.82%), followed by the skin and its appendages (324, 29.19%). Irrational use and intravenous administration were associated with an increased risk of adverse drug events, therefore, surveillance and educational strategies should be strengthened to promote the safety of hepatoprotective drugs. Of the 21 hepatoprotectives, glycyrrhizin, Heluoshugan and Bicyclol were preferable for clinical hepatoprotection, whereas Yinzhihuang, Kuhuang, and ribonucleic acid should be avoided. This parallel approach through spontaneous reporting and drug utilization analyses provided valuable information for the safety of hepatoprotectives, and this synergy should be encouraged to support future pharmacovigilance activities.