Objective: To detect whether suppression of endoplasmic reticulum (ER) stress maintains hepatocyte growth factor (HGF) expression in hepatic stellate cells (HSCs) and its potential mechanism. Methods: Rat hepatic stellate cell line HSC-T6 was treated with the ER stress agonists 5.0 -滋g/mL tunicamycin and 0.2 -滋mol/L thapsigargin, and ER stress inhibitors sodium 4-phenylbutyrate (4-PBA) 4.0 mmol/L and salubrinal 200.0 -滋mol/L were used as pretreatment. Recombinant lentivirus LV-eIf2α-shRNA-GFP was produced to block eIf2α activated by ER stress. Levels of HGF, glucose-regulated protein 78 (GRP78), eukaryotic translation initiation factor 2α (eIf2α), phospho-eIF2α, activating transcription factor 4(ATF4) and C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP) in vitro were measured by quantitative RT-PCR and Western blot. Results: Our results demonstrated that tunicamycin or thapsigargin stimulated GRP78 expression, and activation of ER stress inhibited HGF expression in HSC-T6 cells. The inhibition of HGF could be partly prevented in the presence of 4-PBA or salubrinal, but their effects on ATF4 and CHOP expression were different. Interfering eIf2α mRNA proportionately down-regulated HGF expression. Conclusion: The activation of ER stress inhibits HGF expression of HSCs through decreasing eIF2α expression.