Aim To investigate the role of endoplasmic reticulum stress in adenosine induced HepG2 cell apoptosis.Methods HepG2 cells were treated with different concentrations of ADO for 36 h,and the effect of ADO on cell proliferation was measured by MTT assay.Cell nuclei DAPI staining was used to detect the nuclei change after being treated with different concentrations ADO for 36 h or 2.0 mmol?L-1 ADO for different time.The effect of ADO on HepG2 cell cycle was analysed by flow cytometry after being treated with 2.0 mmol?L-1 ADO for 12 h or 24 h.Translocation of CHOP and Caspase-3 were measured by immunofluorescence after being treated with 2.0 mmol?L-1 ADO for 36 h.The proteins expressions of CHOP,Caspase-4,Caspase-3 and JNK were assayed by western blot.Results The viability of HepG2 cell decreased in a dose-dependent manner;the relative cell viability of 0.5,1,2,4,6 mmol?L-1 decreased by 13.48%?0.12%,27.92%?0.25%,35.21%?0.42%,51.46%?0.24%,71.42%?0.58%,compared with the control group respectively.The nuclei of HepG2 cells treated with different ADO concentrations or 2.0 mmol?L-1 ADO showed condensation,rounding and shrinkage,then fragmentation,which demonstrated cell apoptosis.After being treated with 2.0 mmol?L-1 ADO for 12 h or 24 h,cell cycle analysis showed sub-G1 phase increased;the apoptotic ratio of control,12 h and 24 h was 1.55%?0.12%,10.96%?0.07% and 21.04%?0.26% respectively.Immunofluorescence assay showed the CHOP and Caspase-3 translocation to the nuclei after being treated with 2.0 mmol?L-1 ADO.The expressions of CHOP,Caspase-3 and Caspase-4 increased after being treated with different concentrations ADO for 36 h,while the expression of JNK did not change.Conclusion Endoplasmic reticulum stress is involved in adenosine-induced HepG2 cell apoptosis.