【Abstract】 Objective The purpose of this study is to analyze the relationship between the expression level of Elongator acetyltransferase complex subunit 5(ELP5) in cholangiocarcinoma cells and their proliferation, invasion and metastasis ability, to explore the effect of ELP5 on the survival and prognosis of patients with cholangiocarcinoma. Methods Analyzing the relationship between ELP5 and the prognosis of cholangiocarcinoma patients based on the TCGA database, and plotting of ROC diagnostic curves, cell morphology experiments are employed to analyze the relationship between ELP5 expression and the proliferation, invasion, migration ability in cholangiocarcinoma. Results Differential results shows that ELP5 was highly expressed in cholangiocarcinoma samples, and the overall survival, progression-free survival, and disease-specific survival of patients in the ELP5 low-expression group are significantly higher than those of patients in the high-expression group. It is found that patients in the low ELP5 expression group have significantly longer overall survival, progression-free survival, and disease-specific survival rates compared to those in the high expression group. Univariate and multivariate Cox regression analyses demonstrates that higher ELP5 expression is associated with an increased risk of mortality. Gene enrichment analysis reveals that ELP5 can negatively regulate the ligand binding of G protein-coupled receptor and its signaling process. Morphological experiments with cells indicates that cholangiocarcinoma cells with low ELP5 expression significantly decrease in proliferation, invasion, and migration abilities compared to normal cells. Conclusion Patients with high expression of ELP5 have worse survival prognosis, and the expression level of ELP5 in tissues of patients with cholangiocarcinoma is positively correlates with the risk of mortality. Reducing the expression of ELP5 in cholangiocarcinoma cells can decrease their proliferation and diminish their invasive and metastatic capabilities.