Objective To detect the activation levels of endoplasmic reticulum stress ATF6-CHOP pathway,and to investigate the molecular mechanism of tannic acid (TA) combined with cisplatin (CDDP) against hepatocellular carcinoma.Methods HepG2 cells were cultured with 180 μM TA or/and 0.9 μg/ml CDDP for 24 h or 48 h.The levels of ATF6 (ATF6α),ATF6B (ATF6β) and CHOP were analyzed by real-time fluorescence quantitative PCR (q-RT-PCR) and western blot.Results We found that after 24 h or 48 h,compared with the control group,ATF6 mRNA and protein levels,ATF6B protein level,CHOP mRNA and protein levels were significantly increased in the TA group,CDDP group or combination group (P ＜ 0.01 or P ＜ 0.05).Conclusion TA can combine with CDDP to increase the levels of endoplasmic reticulum stress ATF6-CHOP pathway,and the ATF6-CHOP pathway may be one of the molecular mechanisms synergistic anti-hepatocellular carcinoma effect of TA and CDDP on HepG2 cells.