Despite the oncogenic effects of TRIB3 in multiple malignancies, how TRIB3 is involved in therapeutic resistance remains poorly understood.[23, 24, 25, 26] Interestingly, our results indicated that neither overexpression nor knockout of TRIB3 affected EMT process or migration in hepatoma cells in vitro, although TRIB3 deficiency successfully suppressed sorafenib‐induced lung metastasis in vivo, emphasizing the essential role of in vivo microenvironment in TRIB3‐mediated sorafenib resistance. Here, TRIB3 is linked to hepatocellular carcinoma.