(−)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess bio-activities. In this study, we investigated the protective effects of EGCG against restraint stress (RS)-induced liver injury and immunosuppression. EGCG (10, 20 and 40 mg/kg) was orally administered to mice daily for 7 days before modeling the restraint stress. lood, liver and broncho-alveolar lavage fluid (BALF) samples were collected and tested. We found that EGCG significantly reduced the release of stress hormones to weak restraint stress response. EGCG effectively improved hepatic damage by decreas the serum levels of alanine aminotransaminase (ALT) and aspartate transaminase (AST) in restraint-challenged mice. Furthermore, EGCG also significantly prevented the release of H₂O₂, NOS and 8-isoprostane, and reduced the levels of interleukin (IL)-1β, IL-2,and IL-6 restrained mice. EGCG can normal the level of cytochrome P450 (CYP450) 1A2, 2D22, 2E1 and 3A11 that induced by restraint stress., the inhibition status of T cells subsets in serum and gA in BALF were significantly relieved EGCG pretreatment. Taken together, our data suggest that EGCG possesse hepatic- and immune-protective properties against restraint stress through its anti-oxidant, anti-inflammatory and immunomodulatory activities.