Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with chronic hepatitis C virus (HCV) infection as a major risk factor of HCC. Circulating microRNAs are deregulated in HCC and are candidate biomarkers. The aim of this study was to explore the expression profile of miRNA-122, miR-483, and miR-335 in the serum of HCV-related hepatocellular carcinoma (HCC). 90 HCV-related hepatocellular carcinoma (HCC) patients, 90 non-malignant HCV patients, and 60 healthy controls were included. Serum microRNAs were measured by a qRT-PCR custom array. The expression levels of miR-122 and miR-483 were upregulated in HCC patients, while the miR-335 expression level was downregulated versus controls and HCV groups. Receiver-operating characteristic (ROC) curve analysis was created to examine miRNAs. miR-483 presented the best diagnostic potential because it showed the highest diagnostic accuracy for distinguishing HCV-related HCC patients from controls (AUC = 0.98) with 100% sensitivity. Moreover, there was obvious prognostic power in distinguishing HCV from HCC (AUC = 0.95) with 88% sensitivity. In conclusion, studied microRNAs (miR-122, miR-483, and miR-335) could serve as potential non-invasive early diagnostic biomarkers for HCC, and we identified a panel of three serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.