Objective To investigate the effect of parthenolide ( PTL) and PKC inhibitor on human gastrointestinal stromal tumor (GIST) cell proliferation and apoptosis and the mechanism involved .Methods Human GIST cell lines were cultured in vitro, and the cell proliferation rate of GIST , was determinate by MTT;flow cytometry was used to test the early apoptosis rate of GIST;Western blot assay was applied to detect the expression of endoplasmic reticulum stress-related proteins , GRP78 and GADD153.There were four groups: control group , PTL group, PKC inhibitor group , combine PTL and PKC inhibitor group .Results PTL and PKC inhibitor combination therapy for GIST was sig-nificantly more effective than a single-drug therapy (P<0.05);as for the early apoptosis rate , the combination ther-apy for GIST cells was significantly higher than that medication alone group (P<0.05).the expression of endoplas-mic reticulum stress-associated protein GRP 78 and GADD153 was obviously higher in PTL and PKC inhibitor combi-nation group than that in medication alone group (P<0.05).Conclusions PTL and PKC inhibitor combination therapy for GIST cells can induce apoptosis , which is possibly mediated via endoplasmic reticulum stress pathway .