Objective:To study the effects of mda-7/IL-24 on the growth,proliferation,apoptosis of different hepatic carcinoma cell lines and the related mechanisms.Methods: A recombinant adenovirus Ad-mda-7 was constructed and was used to transfect human hepatic carcinoma cell lines (HepG2,Hep3B and PLC/PRF/5) and normal liver cell line L02.MTT assay and FACS were employed to assess the growth and apoptosis of cells; the expression of related protein expression was examined by Western blotting.The cells were treated with calpastatin Ⅰ (ALLN,25 μmol/L) for 30 min to block the endoplasmic reticulum stress (ER-stress) and the above indices were examined again.Results: Treatment with Ad-mda-7 resulted in selective inhibition of cell proliferation and induced apoptosis,especially in HepG2 cells; Ad-mda-7 showed no influence on normal cells. Pretreatment with ALLN partially inhibited the above effects of Ad-mda-7.Western blotting revealed that Ad-mda-7 induced up-regulation of BiP/GRP78 and Bax protein,activation of caspase-12,caspase-3 and phosphorylation of p38 MAPK in HepG2 cells.Blocking ER-stress with ALLN down-regulated Bax,caspase-12 expression and inhibited activation of caspase-3 and caspase-12,but showed no effect on the expression of BiP/GRP78 or phosphorylation of p38 MAPK.Conclusion: mda-7/IL-24 can cause growth inhibition and promote apoptosis of hepatic carcinoma cells through the ER-stress pathway.