To the best of our knowledge, this retrospective study is the first to report the efficacy and safety of a novel triple combination therapy with FOLFOX-HAIC, lenvatinib plus PD-1 inhibitor, which yielded a promising antitumor activity with manageable safety profiles in patients with locally advanced and metastatic iCCA. The gene discussed is PDCD1; the disease is infantile convulsions and choreoathetosis.