The extraction process on total phenolic acids from Lethariella spp.was optimized using Box-Behnken design.The result showed that the highest yield of total phenolic acid was 13.43±0.56 mg/g (n = 3) under the optimal extraction condition that the liquid to solid ratio was 30 mL/g,the ethanol concentration was 82%,and the extraction time was 1.8 h.In vivo antioxidant assays demonstrated that total phenolic acids from Lethariella spp.could scavenge DPPH free radical to some degree and also possess a certain total reducing power.Moreover,the total phenolic acids extract could significantly increase the survival rate (15.73%±4.89%,P< 0.01) ofCaenorhabditis elegans under thermal stress at 0.05 mg/mL.The finding suggested that the total phenolic acids extract from Lethariella spp.was a potential natural antioxidant that could be developed into a novel functional product.