Mechanistically, sorafenib can induce autophagy in HCC cells through multiple ways, such as promoting IRE1 signals (Shi et al., 2011), activating Akt pathway (Zhai et al., 2014), suppressing mTORC1 (Shimizu et al., 2012), or inhibiting STAT3/Mcl-1/Beclin 1 axis (Tai et al., 2013), and so on. Here, ERN1 is linked to hepatocellular carcinoma.