Objective:To investigate the protective effects of Ganoderma lucidum spore polysaccharide(GLSP)on liver injury caused by acetaminophen(APAP).Methods:Fifty mice were randomly divided into five groups:Blank group,model group,positive drug group,GLSP low-dose group and GLSP high-dose group,with 10 mice in each group.After each group was pre-administered according to the corresponding dose for 14 consecutive days,the liver index,serum indexes(glutamic oxalacetic transaminase(AST),glutamic-pyruvic transaminase(ALT))and liver tissue plasma indexes(glutathione(GSH),malonaldehyde(MDA),superoxide dismutase(SOD),Caspase-3,Bax and Bcl-xl)were determined.Results:Compared with the blank group,ALT,AST,MDA and proapoptotic genes Caspase-3 and Bax were very significantly increased in the model group(P<0.01).The contents of SOD and GSH decreased very significantly(P<0.01),and HE staining showed that APAP treated mice showed typical lobular central necrosis of liver.Compared with model group,ALT and AST were very significantly decreased in polysaccharide dose group(P<0.01),SOD and GSH were significantly increased(P<0.05)and MDA was significantly decreased in polysaccharide low-dose group(P<0.05),SOD and GSH were very significantly increased(P<0.01)and MDA was very significantly decreased in polysaccharide high-dose group(P<0.01),and pro-apoptotic genes Caspase-3 and Bax were very significantly decreased in polysaccharide group(P<0.01),and the liver histopathological observation showed that the necrotic area of liver tissue decreased.Conclusion:Ganoderma lucidum spore polysaccharide can preprotect APAP liver injury,and its mechanism may be related to improving the antioxidant capacity of liver and inhibiting the occurrence of apoptosis.