a1, 2-Mannosidases key enzymes in N-glycan processing and located both in the endoplasmic reticulmu and golgi, have been targets in the development of anti cancer therapies. Previous studies have shown its involvement in protein degradation. In this study 1-deoxymannojirimycin, a specificinhibitor of a1, 2-mannosidase and generating high mannose type of N-glycan, was treated in human hepatocarcinoma 772I cells and lnduced the endoplasmic reticulum strss. Key moleculars as XBPl and GRP78/Bip were activated and up-regulated, which suggested the UPR pathway was activated. The cleavage of caspase-12, -9 and-3 was also detected, which impli-caled the ER stress was triggered and apoptosis occurred in H7721 cells. The results lndlcare the high Man structure generated by 1-deoxymannojirilnyein may constitute potential novel mechanism fol ER slress and caspase-12 pathway of cell apoptosis.