Abstract: Objective Cordycepin is the active component of Cordyceps sinensis and Cordyceps militaris,belongs to Traditional Chinese Medicine,and has a significant anti-cancer activity.This research aimed to study the roles of cordycepin in inducing apoptosis of cutaneous T-cell lymphoma Hut78 cell line.Methods After treatment with 5 μg/ml cordycepin for 24 hours,the proliferation and apoptosis of Hut78 cells induced by cordycepin were analyzed via MTT and flow cytometry assay,respectively,qRT-PCR and Western blotting were used to investigate the levels of apoptosis-related proteins.Results Proliferation and apoptosis of Hut78 cells were inhibited by cordycepin in a dose-dependent manner.The expression levels of apoptosis-related proteins including caspase-8,cleaved caspase-3,tBid,Bax,Apafl,AIF and DR3 receptor were all decreased in the cells stimulated with 5 μg/ml cordycepin for 24 hours compared with those in the control group.Conclusion Cell proliferation and induced apoptosis could be inhibited by cordycepin via the DR3/mitochondrial signaling pathway.