Aims and ObjectivesHepatitis C virus (HCV) infection is a significant risk factor for the development of hepatocellular carcinoma (HCC). Serum‐derived circular RNAs (circRNAs) play several crucial roles in HCV and HCC. They represent a promising area of research for improving the diagnosis and understanding the mechanisms of HCV‐HCC. This study aims to identify a serum‐derived circular RNA (circRNA) diagnostic panel for HCV‐HCC and to elucidate the regulatory mechanisms underlying their role in cancer progression.MethodsIn this study, data mining and in silico analysis were conducted to identify the role of circular RNAs (hsa_circ_0003288, circ‐RNF13, hsa_circ_0004277, circANRIL, circUHRF1, hsa_circ_103047) and their associated biomarkers (IL‐6 and NF‐κB) in HCV‐HCC pathogenesis. Additionally, RT‐PCR was performed to assess their expression levels across different study groups (G0 = control, G1 = HCV, G2 = HCC, and G3 = HCV‐induced HCC).ResultsThe expression levels of circular RNAs, including hsa_circ_0003288, circ‐RNF13, hsa_circ_0004277, circANRIL, circUHRF1, and hsa_circ_103047, as well as the biomarkers IL‐6 and NF‐κB, were significantly elevated in the G3 group compared to the G0 group. ROC analysis also revealed significantly different expression rates for G3 group and G0 group.ConclusionThe data revealed that cricRNAs panel (hsa_circ_0003288, circ‐RNF13, circANRIL, circUHRF1, and hsa_circ_103047) could serve as a diagnostic biomarker and therapeutic target for HCV‐induced HCC.