Background: The incidence of patients with Cholangiocarcinoma(CCA) as most prevalent primary biliary and hepatic malignancyhas increased in the recent years. CCA was known asaggressive cancer because it survival time is less than ۲ years.The surgery or liver transplantation is the only effective therapyfor early-stage patients but unfortunately, most of them diagnosedat the advanced stages. The sensitivity and specificity ofserum markers that frequently used in clinical such as carbohydrateantigen۱۹-۹ (CA۱۹-۹) and CA-۱۲۵ have lack of sensitivityand make mistake in treatment trend. In this study, weconsiderate Long non-coding RNA (lncRNA) as a member ofnon-coding RNA which exists in the nucleus and cytoplasm thathave a length more than ۲۰۰ nucleotides, as a novel biomarkerfor early detection of CCA. Today's many studies showed thatlncRNA have important roles in Some functions such as regulatingthe post-transcriptional processing, splicing, transport,translation, and degradation processes of mRNA. Moreover,lncRNAs are closely associated with proliferation, migration,invasion, and tumor development, as a high expression of lncRNAsin some carcinoma promotes cancer to advance stages.Therefore, lncRNAs’ different expression between tumoral tissuesand normal ones can be used as a biomarker for early detectionof cholangiocarcinoma.Materials and Methods: In this systematic review study, anextensive English-language literature search was conductedusing NCBI, ScienceDirect to identify original studies andreview articles, according to keywords: Cholangiocarcinoma,Biomarkers and Long non-coding RNA till January ۲۰۱۸. Thepapers collected and then was ranking based on appropriate criteria.A total the ۳۱ eligible studies were selected according tothe keywords mentioned in the molecular field of cancer-relatedto Cholangiocarcinoma.Results: After completing the final analysis, ۲۶ studies fromother research that were more relevant to this subject, were assessedand diagnostic accuracy lncRNAs were pooled using the“LncRNAs Disease databases”.Conclusion: According to the limited number of studies regardingthe role of lncRNA in CCA, more studies will be neededin the future to demonstrate the importance of lncRNA intumor initiation, invasion and metastasis, as well as their utilityas therapeutic targets. Moreover, considering that lncRNAhas been detected in pathological pancreatic tissues till now,the investigation in “easy access” samples like blood for thefuture will make them even more attractive and less invasivebiomarkers.