Treatment of HCC cells with the Insig1/2 loop 1 peptide disrupted the IGF1‐induced PCK1‐Insig1/2 interaction, PCK1‐mediated phosphorylation of Insig1 at S207 and Insig2 at S151, nuclear accumulation of SREBP1, SREBP1 activity, downstream lipid synthesis gene expression, lipid accumulation, and tumor cell proliferation. The gene discussed is INSIG2; the disease is hepatocellular carcinoma.