In general, our study firstly determined the synergistic effects of ABT-737 plus Celastrol in human hepatocellular carcinoma cells, opening the opportunity of combining these two agents as potent therapeutic combination, and implying that the activation of ER stress which lead to the manipulation on Noxa might served as a effective strategy to inhibit Mcl-1 and thus to increase the anti-cancer activities of ABT-737. Here, PMAIP1 is linked to cancer.