DEAE C-52 cellulose anion exchange chromatography was used to fractionate and purify the fucoidan from Sargassum henslowianum. The highest yielding fraction was named HF1. And free radical oxidative degradation was used to obtain HDF1 and HDF2. The higher HDF2 was separated and purified using Superdex 75 gel column chromatography to obtain HDF21 and HDF22 components. HepG2 cells were cultivated in vitro and it were affected with different concentrations of each component to determine the intracellular cholesterol content. The results showed that after degradation, the polysaccharide content, sulfate content and fucose content of HDF1 were higher than HF1, but the uronic acid content was lower than HF1. The degradation had the greatest influence on the chemical composition of HDF21. The four components of HF1, HDF1, HDF21 and HDF22 could reduce the intracellular cholesterol content after HepG2 cells were treated, and the best effect was at high concentration (500 μg/mL). After 72 hours of treatment in high concentration group, the intracellular cholesterol content was decreased most significantly (P<0.01), and HDF21 had the best cholesterol-lowering effect.