During the last decade, microRNAs (miRNAs) have been identified as potential biomarkers and therapeutic targets for multiple malignancies; yet, few studies exist on intrahepatic cholangiocarcinoma (ICC). In the present study, a miRNA microarray was applied to determine the significant miRNAs involved in ICC. miR-150 was found to be significantly downregulated in ICC. We further enrolled 15 ICC patients who received radical resection to test these findings in plasma. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we examined and quantified the expression levels of miR-150 in tumor tissues, peritumoral noncancerous tissues and blood samples of 15 ICC patients. The diagnostic value of plasma miR-150 for differentiating patients with ICC from the age- and gender-matched controls was analyzed. For plasma samples, compared with normal controls, the level of miR-150 expression was found to be upregulated (P<0.010) in ICC patients. While differentiating ICC from normal controls, receiver operator curve (ROC) analysis of plasma miR-150 revealed the area under the curve (AUC) of 0.764 (P<0.010) with sensitivity of 80.6% and specificity of 58.1%. The diagnostic value of carbohydrate antigen 19-9 (CA19-9) and the combination of miR-150 and CA19-9 were also evaluated. We found that the combination of these two markers improved the power of screening ICC. Moreover, on the basis of the plasma miR-150 level, 15 ICC patients were divided into a low or high expression group. We found that plasma miR-150 is a potential diagnostic biomarker for ICC.