Objective: Polygoni Multiflori Radix (PM) is a traditional herbal medicine with repeated reports of liver injury events in recent years. We wondered whether the classical processing method, namely, nine?time steaming and sun drying (NSSD), had toxicity?attenuating effects on PM and the relationships between toxicity and times of processing, as well as with the alteration trends of its compounds. Materials and Methods: The chemical fingerprints of different PM extracts were developed using ultra?high?performance liquid chromatography. The spectrum?toxicity correlation between the chemical fingerprints and hepatocellular toxicity was analyzed with multiple correlation analysis. Results: The results suggested that the hepatotoxicity of NSSD processing products markedly decreased with the repeated steaming and sun drying, which was obviously superior to the product processed by the modern method. Comprehensive analysis revealed that the contents of cis?stilbene glycoside and emodin?8?O?β?D?glucoside related to liver injury susceptibility were reduced with the times of NSSD processing, which was consistent with the decreased trend of hepatocellular toxicity. After the five times of NSSD, the contents of them as well as the hepatotoxicity of PM were steady. Moreover, we found that the contents of catechin and physcion declined rapidly after the one time of NSSD and then remained stable until the nine times of NSSD. Based on the fact, they could be utilized to indicate whether PM products were processed by steaming and sun drying. Conclusions: This paper confirmed that the NSSD had a good influence on the toxicity attenuating to PM and found four compounds which could apply for the quality control of PM.