To research the preliminary characterizations, antioxidant and hepatoprotective activity of polysaccharides from Cistanche deserticola (CDPs), three polysaccharide fractions, CDP-A, CDP-B and CDP-C, were obtained by successively membrane filtration (microfiltration, ultrafiltration and nanofiltration). Molecular weights, monosaccharide compositions, purities and IR spectra of the three fractions were analyzed. Results showed that CDP-C contained higher proportion of galacturonic acid (GaIUA) than CDP-B and CDP-A. Antioxidant activities were also analyzed and the results revealed that CDP-C possessed the highest activity. Thus, hepatoprotective activity of CDP-C was studied further. In vitro research, CDP-C promoted viability of HepG2 cells. In vivo research, CDP-C ameliorated the alterations induced by alcohol, including serological indexes (alanine transaminase, acid phosphatase, gamma-glutamyl transpeptidase and triglyceride) and hepatic indicators (superoxide dismutase, malondialdehyde, glutathione S-transferase and triglyceride) in model animals. The prominent microvesicular steatosis and mild necrosis in hepatic histopathology of model animals were also attenuated by CDP-C administration. These findings indicated that CDP-C possessed hepatoprotective activity against chronic hepatic injury induced by alcohol. The underlying mechanism might be that CDP-C can reduce the contents of MDA and TG, and modulate the activities of the relative enzyme. This property might associate with GaIUA in CDP-C. (C) 2016 Published by Elsevier B.V.