After EPI treatment, the apoptosis rates of HepG2shCtrl and Bel‐7402shCtrl cells were significantly increased to 50.36 and 41.59%, and the apoptosis rates of HepG2shMus81 and Bel‐7402shMus81 cells were further increased to 85.17 and 59.78%, indicating that Mus81 knockdown could significant promote the cytotoxity of EPI to HCC cells. Here, MUS81 is linked to hepatocellular carcinoma.