Given that SIRT1 is a promising regulator of metabolism and autophagy (Bellet et al., 2016; Ou et al., 2014), which are also significant for MDR in cancer cells (Bhattacharya et al., 2016), it is important to further explore the mechanism of USP22/SIRT1‐induced MDR in HCC cells. Here, SIRT1 is linked to hepatocellular carcinoma.