Recent studies have demonstrated that upregulation of BCAT1 and reprogramming of branched‐chain amino acid metabolism in non‐small cell lung cancer cells attenuates ROS accumulation and mediates resistance to EGFR TKIs.[37] UBQLN1 upregulation in hepatocellular carcinoma cells induces PGC1β degradation in a non‐ubiquitinating manner to reduce ROS production after sorafenib treatment, leading to sorafenib resistance.[38] Our study further proved that HECTD2 was responsible for lenvatinib resistance by attenuating oxidative stress and reducing ROS production. Here, PPARGC1B is linked to hepatocellular carcinoma.