To explore the underlying mechanism by which CD73 promotes iCCA progression, we performed RNA-seq analysis and western blot assays and found that CD73 overexpression in iCCA cells activated several downstream signaling pathways, such as the AKT/GSK3β/β-catenin signaling, which is known to promote proliferation, invasion, and migration of malignant cells and mediate tumor immune evasion. The gene discussed is AKT1; the disease is neoplasm.