A novel alkali-soluble polysaccharide from Lepista sordida (LSAP) mycelia with antioxidative and hepatoprotective activities was characterized. The weight-average molecular weight and number-average molecular weight of LSAP were 1.442 × 103 and 6.05 × 102 kDa, respectively. LSAP was consisted of glucose (57.9%), xylose (31.8%), and small amounts of rhamnose, arabinose, galactose, glucuronic acid, and galacturonic acid (1.2%–3.1%). The FT-IR and 2D NMR confirmed that LSAP was composed of Xylp, Araf, 4-O-Me-α-D-GlcpA, (1→4)-linked β-D-Glcp, and (1→4)-α-D-GalA, and β-glycosidic linkages between these sugar units. LSAP displayed notable effects on 1,1-dephenyl-2-picryhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, lipid peroxidation inhibitory ability, reducing power and Fe2+ chelating property. These biological effects were further verified by suppressing CCl4-induced oxidative liver damage in mice at doses of 100 and 200 mg/kg. Administration of LSAP in mice prior to CCl4 significantly prevented the CCl4-induced elevation in serum alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde. Mice treated with LSAP demonstrated to increase activities in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver. We also found out that LSAP prevented CCl4-induced oxidative liver histological alteration. LSAP may exert hepatoprotective effects against CCl4-induced damage through antioxidant mechanisms in model mice.