Polygonum multiflorum Thunb. (HSW) is widely used as herb medicine and health food additive. Recently, a series of HSW-induced hepatotoxicities have been reported and many studies have been carried out to investigate it. But contradictory conclusions were drawn that might be caused by the inconsistent quality of market decoction pieces. Therefore, the HSW decoction pieces quality was evaluated with a developed novel method in the paper. 25 batches of raw HSW (RHSW) and 21 batches of processed HSW (PHSW) samples were purchased from different provinces of China. HPLC determination was performed to identify and detect the contents of 16 chemical compounds in herbal material. Fingerprint similarity was analyzed using chromatography information and the results showed that most herbs were in good similarity. Then, a comprehensive evaluation strategy based on principal component analysis with representative quality control indicators was developed to evaluate the quality of HSW samples. And the rationality of the developed method was verified by HCA analysis. The results showed that the herb from Dabashan, Sichuan Province, no matter RHSW or PHSW had the best quality. Different representative components were selected for RHSW or PHSW decoction pieces which might be caused by the chemical reaction during processing. And most PHSW were unqualified according to the requirement of Chinese Pharmacopeia which might take the responsibility for the toxicity of HSW.