Background: Chronic infection with hepatitis B virus (HBV) is related to more than 50% of all cases of hepatocellular carcinoma (HCC). The HBx protein of the virus plays an important role in carcinogenesis through different mechanisms, including interaction with the Notch1 signaling pathway. Several microRNAs have also been shown to play essential roles in the carcinogenesis of HCC, and the molecules can be considered the novel biomarkers for the DIAGNOSIS of different types of cancer. Methods: In the present study, the expression levels of four bioinformatically predicted microRNAs, including miR-214, miR-6510, miR-5193, and miR-34a, were compared in individuals with HBV-associated HCC and controls in order to assess the diagnostic utility of these microRNAs as noninvasive biomarkers. Seventy three plasma samples were subjected to RNA extraction, and the microRNA expression profiles were assessed by RT-qPCR. The expression of miR-103 was used as the endogenous reference for the normalization of quantitative data. Results: The plasma expression of all miRNAs was significantly lower in the HCC group, but the downregulation was most marked for the newly described molecule, miR-5193 (-18. 86 folds and-5. 71 folds compared to healthy individuals and chronic HBV patients). Another novel microRNA, miR-6510, was downregulated by-4. 23 folds (P = 0. 001). The results of the ROC curve analysis indicated that the differential expression of miR-5193 could distinguish HCC patients with high sensitivity and specificity. Conclusions: The study microRNAs may have a role in HCC development and progression. In addition, miR-5193 can be potentially used as a non-invasive biomarker for the detection of HBV-induced HCC.