Background: Pentraxin 3, referred to as tumor necrosis factor-stimulated gene 14, is an elongated pentraxin that belongs to the pentraxin superfamily. Objectives: To evaluate the clinical significance and potential role of Pentraxin 3 as a maker for diagnosis of hepatocellular carcinoma (HCC) related to HCV infection. Subjects and methods. The study included 78 patients and 26 healthy individuals from Man-soura University Hospital. Participants were divided into three groups: healthy individuals without HCV, chronic HCV patients with cirrhosis, and HCC patients with HCV. Pentraxin-3, AFP, and DCP levels were measured using ELISA. Diagnostic accuracy was evaluated using receiver operating characteristic curve analysis. Results: Pentraxin 3, AFP and DCP levels were significantly higher in cirrhosis and HCC patients compared to the healthy group, with HCC patients showing higher levels than cirrhosis patients. The ROC curve analysis for differentiating HCC from the healthy group revealed that, a cut-off value of 0.848 for Pentraxin 3 had superior sensitivity and specificity (81.8% and 88.5%, respectively), followed by DCP (81.8% and 73.1%, respectively) however, AFP had the lowest sensitivity and specificity. The combination of these three markers showed the highest sensitivity and specificity (95.5% and 96.2%, respectively). In distinguishing HCC from the cirrh-osis group, a cut-off value of 0.879 for DCP exhibited superior sensitivity and specificity (81.8% and 88.0%, respectively) followed by Pentraxin 3 (72.7% and 84.0%, respectively) however, AFP showed the lowest sensitivity (54.5%) and highest specificity 84.0%. The combination of these three markers showed the highest sensitivity and specificity (90.9% and 96.0%, respectively) in discriminating between HCC and cirrhotic groups, with an excellent AURC of 0.973. Conclusion: Pentraxin 3 is potential good a maker for diagnosis of HCC related to HCV infection.