In this study,HepG2 cells and Caenorhabditis elegans were used as models to study the antioxidant capacity of Lethariella spp. ethanol extract (LEE) and its possible mechanism of action.The results showed that 400-800 μg/mL LEE can effectively increase the cell viability of HepG2 cells and reduce cell apoptosis on the oxidative stress induced by acrylamide.In the in vivo environment,LEE exhibited an excellent potential protection on C. elegans against oxidative stress.0.01 mg/mL LEE showed no negative effect on the growth and reproduction of nematodes.Under thermal stress,the mean survial of wild-type N2 nematodes pretreated with LEE was prolonged by 23.33% from 10.00 ± 0.00 h to 12.33 ± 0.58 h.However,LEE failed to extend the survivals of age-1,daf-2 and daf-16 mutant nematodes under heat stress.In summary,LEE possesses a promising anti-oxidant biological activity in vivo and in vitro,and its mechanism of action may depend on the three genes of age-1,daf-2 and daf-16  in the insulin signaling pathway.