Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy in the liver, which is associated with a poor prognosis. However, the molecular pathogenesis of iCCA remains unclear. RNA-Seq for tumor and para-tumor sample pairs enables the characterization of changes in the gene expression profiles of patients with iCCA. The present study analyzed RNA‑Seq data of seven iCCA para‑tumor and tumor sample pairs. Differential gene expression analysis demonstrated significant upregulation of PDZK1IP1, EEF1A2 and RPL41 (ENSG00000279483) genes in the iCCA samples when compared with the matched para‑tumor samples. Furthermore, genes associated with the immune system, metabolism and metabolic energy were significantly downregulated in the iCCA tumor tissues, indicating that this is involved in the pathogenesis of iCCA. The present study aimed to elucidate the gene expression patterns associated with the tumorigenesis of iCCA by comparing tumor and normal tissues, in order to isolate novel diagnostic factors for iCCA.