By retrieving domestic and foreign literatures, the authors provided a systematic review for effects of Xanthii Fructus, toxicity recorded in ancient/current literatures and relevant toxicological experience, and summarized clinical characteristics of clinical cases related to Xanthii Fructus and influencing factors. In addition to liver and kidney injuries as the major side effects of Xanthii Fructus, neurotoxicity and cardio-toxicity of Xanthii Fructus were also common clinical adverse events. However, there have been a few animal experimental studies so far. Oral administration and external application with Xanthii Fructus have often caused skin reactions, even such severe cases as exfoliative dermatitis. The authors suggested standardizing the clinical medication, avoiding to use untreated prescriptions and unprocessed herbs, ensuring the effective and safety use of Xanthii Fructus in strict accordance with the recommended dosage and usage in pharmacopeia, paying attention to the accumulation of safety signals, strengthening studies on toxic substance, toxicity mechanism, and synergy and attenuation effects.