Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide. Long noncoding RNA (lncRNA) contribute to extensive biological processes and play oncogene or tumor suppressor roles in several diseases. Objective: To evaluate the expression levels of lncRNA AFAP1-AS1 in Egyptian patients with chronic hepatitis c virus infection (HCV) and to assess its relations with clinicopathological features of HCC. Patients and Methods: 60 chronic hepatitis C (CHC) patients in addition to 40 healthy subjects as a control group were enrolled in this study. CHC patients were divided into three groups, group I comprised 33 patients with chronic hepatitis C (CHC); group II comprised 15 patients with cirrhosis and 12 patients with HCC. lncRNA AFAP1-AS1 relative expression level was determined by RT-PCR. Results: lncRNA AFAP1-AS1 relative expression level was upregulated in CHC groups (4.28 ± 2.69) compared to controls [(2.56 ± 1.35), P < 0.001*]. Additionally, there was a significant difference between case groups as the highest relative expression level was in HCC patients (5.3 ± 2.28) compared to cirrhosis (4.28 ± 3.69) and CHC (3.93 ± 0.652). The lncRNA AFAP1-AS1 relative expression level was significantly positively correlated with clinicopathological features of HCC. Conclusions: lncRNA AFAP1-AS1 relative expression level was upregulated in CHC patients in particular patients with cirrhosis and HCC. Thus, circulatory lncRNA AFAP1-AS1 may be able to serve as a promising non-invasive diagnostic marker for cirrhosis and HCC.