Abstract Background The intensive interplay between aberrant epigenetic events and metabolic remodeling represents one of the hallmarks of tumors, including colon cancer. The functions of Bromodomain Containing Protein BRD‐9 in colon cancer remains indefinite. We aimed to identify the biological roles and clinical significance of BRD9 in colon cancer. Methods The univariate‐ and multi‐variate Cox regression models were used to screen risk epigenetic regulators. Kaplan–Meier analysis and Pearson correlation analysis were used to assess clinical significance of BRD9. CCK‐8 assays, colony formation assay, Transwell, and soft‐agar assay were performed to determine the in vitro roles of BRD9. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of colon cancer cells were evaluated by a Seahorse XF Extracellular Flux Analyzer. In vivo models and RT‐qPCR, western blotting, and Chromatin Immunoprecipitation (ChIP) assay were conducted to explore the functional roles of BRD9 in COAD. Results In the study, we detected the expressions of 662 epigenetic regulators in COAD and identified a series of 42 hazard epigenetic factors with p