Cholangiocarcinoma, ranking as the second most prevalent primary hepatic malignancy following hepatocellular carcinoma, is distinguished by its aggressive invasiveness and grim prognosis. Over the past decade, chemotherapy has persisted as the standard first-line treatment for cholangiocarcinoma; However, the outcomes in terms of efficacy and patient survival have remained disappointingly suboptimal due to the emergence of chemotherapy resistance issues. Thus, a newer and deeper understanding of pathways to regulate cholangiocarcinoma progression and sentisize chemotherapy therapy is needed. Metabolic reprogramming is a hallmark of cancer, intricately linked to post-translational modifications . The critical role of novel acyl modifications in tumorigenesis has garnered widespread attention in recent years . Succinylation, a new post-translational modification occurring on lysine residues, is involved in many core energy metabolic pathways, including the tricarboxylic acid cycle and glucose metabolism, and plays a role in regulating the progression of various tumors. In this study, from the perspective of succinylation modification, we explore a novel mechanism of cholangiocarcinoma progression and proposed a new direction for sensitized chemotherapy treatment.