Chronic exposure to arsenic over a period of time induces toxicity, primarily in the liver but gradually in all systems of the body. Morin hydrate (MH; 2′,3,4′,5,7-pentahydroxyflavone), a potent flavonoid abundantly present in plants of the Moraceae family, is thought to be a major bioactive compound that may be used to prevent a wide range of disease pathologies including hepatotoxicity. Therapeutic applications of morin (MOR) are however seriously constrained because of its insolubility, poor bioavailability, high metabolism and rapid elimination from the human body. Nanoformulation of MOR is a possible solution to these problems. In the present study we investigated the effectiveness of morin encapsulated chitosan nanoparticles (MCNPs) against arsenic induced liver damage in mice. MNCPs with an average diameter of 124.5 nm, a zeta potential of +16.2 mV and an encapsulation efficiency of 78% were prepared. Co-treatment of MOR and MCNPs by oral gavage on alternate days reduced the serum levels of AST, ALT, and ALP that were elevated in arsenic treated mice. The efficiency of MCNPs was found to be nearly 4 times higher than that of free MOR. Haematological and serum biochemical parameters including lipid profiles altered by arsenic were normalized following MCNP treatment. Arsenic deposition was lowered in the presence of MCNPs. Administration of MCNPs markedly inhibited ROS generation and elevated MDA levels in arsenic exposed mice. The level of hepatic antioxidant factors such as nuclear Nrf2 (Nrf2), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), GSH peroxidase (GPx), glutathione-S-transferase (GST), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1(NQO1) were markedly enhanced in the arsenic + MCNP group. Treatment by MCNPs prevented the arsenic induced damage of tissue histology. Also, MCNPs suppressed the arsenic induced pro- and anti-apoptotic parameters and attenuated the level of inflammatory mediators. Our data suggest that MCNPs are good hepatoprotective agents compared to free morin against arsenic induced toxicity and the protective effect results from its strong antioxidant, antiapoptotic and anti-inflammatory properties.