Mechanistically, CXCL6 regulated the CXCR1/2‐JAK‐STAT/PI3K axis in CCA via autocrine signaling, leading to lipid metabolic reprogramming, and promoted neutrophil extracellular traps (NETs) formation by activating the RAS/MAPK pathway in neutrophils. This evidence concerns the gene CXCR1 and cholangiocarcinoma.