In an attempt to validate the aforementioned theoretical hypothesis, we explored the cytotoxic and therapeutic effects of lenvatinib on HCC cells with CREB3L2 knockdown or overexpression, and the effect of different concentrations of lenvatinib was assessed in primary resistant cell line MHCC97H or sensitive cell line Huh7 [21]. Here, CREB3L2 is linked to hepatocellular carcinoma.