In summary, our study provides valuable insights into the use of ANXA1 as a scaffold protein to promote tumor occurrence and development through metabolic adaptation and confirms the tumor suppressive effect of ANXA1 inhibition combined with glutamine deprivation in vitro and in vivo, which has important therapeutic potential for intrahepatic cholangiocarcinoma. The gene discussed is ANXA1; the disease is intrahepatic cholangiocarcinoma.