Perilla frutescens var. frutescens is an economically important crop-a widely used herb that has been cultivated in China for over 2000 years. A novel polysaccharide (PFP) was extracted from P. frutescens var. frutescens and purified by the Sevag method and Sephadex G-200 gel chromatography. Its structural characteristics and antitumor activity were investigated. Total sugar, uronic acid, and protein contents in PFP were 89.73%, 8.93%, and 1.56%, respectively, and its molecular weight was 1.18 x 10(6) Da. FT-IR, ion chromatography and NMR showed that PFP was a pyranose consisting primarily of rhamnose, arabinose, galactose, glucose, xylose, and galacturonic acid, at molar ratios of 0.13: 0.55: 1.40: 1.00: 0.13: 0.22 with alpha- and beta-type glycosidic residues, its main chain may consists by alpha-L-Araf-(1 ->,-> 6)-beta-D-Galp-(1 ->,-> 4)-alpha-D-Glcp-(1 ->,-> 1,4)-beta-D-Xylp(1 ->,-> 4)-alpha-GalpA-(1 ->,-> 2,4)-alpha-L-Rhap-(1 ->. PFP inhibited tumor proliferation and reduced mitochondrial membrane potential in vivo in H22 tumor-bearing mice by blocking the cell cycle S phase. PFP also exhibited protective effects on mouse liver and thymus tissues. These findings provide a theoretical basis for the development of safe and effective natural anti-liver cancer drugs from novel polysaccharides produced by PFP.