Abstract: OBJECTIVE To investigate the liver protection of nucleobases from Ruditapes philippinarum in vivo and in vitro. METHODS CCK-8 assay was used to detect cell viability. The model of carbon tetrachloride(CCl4) and hydrogen peroxide(H2O2)-induced chemical liver injury in primary cultured hepatocytes were prepared in vitro. The model of carbon tetrachloride and D-galactose-induced liver injury in mice were built in vivo. The levels of ALT， AST， MDA， SOD and GSH-Px activities were measured to evaluate liver protection of nucleosides from Ruditapes philippinarum. RESULTS The nucleoside of Ruditapes philippinarum significantly increased the survival rate of liver cells. The drug groups significantly decreased the activities of AST and ALT， significantly increased the activity of SOD and significantly reduced the level of MDA. CONCLUSION Nucleosides from Ruditapes philippinarum show hepatoprotective effects on CCl4-induced chemical liver injury， D- galactose induced aging， and liver cells injured by CCl4 and H2O2. This study provided experimental data for the development and utilization of Ruditapes philippinarum resources and new hepatoprotective medicines.