Abstract: There were many studies for the removal of polyphenols in beverage and food industries which used fresh plant-derived natural products as raw materials. Most of the studies had used the percentage as an indicator to assess the removal of polyphenols and there was a rare study to use any toxicological indicator to evaluate the removal of plant-derived polyphenols. This study used PVPP to remove polyphenols from water extracts of fresh hickory nuts and a neuronal cell model to test cytotoxicity of polyphenols for evaluation the efficiency of polyphenol removal by PVPP. Data showed that PVPP treatment could significantly remove polyphenols and the efficiency of removal reached at 84.6% when 40 mg PVPP was used to treat the water extract from 500 mg of fresh hickory nuts for 10 min. The efficiency of polyphenol removal was further confirmed by observation of neuronal cell morphology with fluorescence microscopy and determination of cell viability with MTT assay. Data showed that the extract without PVPP treatment significantly(p <0.01) induced cell death in both SH-SY5Y-EGFP tumor cell line and HUVEC primary cell cultures in a dose-dependent manner. In contrast,the extract with PVPP treatment had no significant influence on viability of both SY5 Y cells and HUVEC cells. These results suggested that the extract from hickory nuts contains polyphenols had showed a significant cytotoxicity to both tumor cells and normal cells. PVPP treatment could efficiently remove polyphenols and significantly reduced cytotoxicity of water extract from hickory nuts.