The use of noninvasive surrogate blood biomarkers for the assessment of liver fibrosis has gained increasing interest. In this study, 88 chronic hepatitis C patients (aged 21–68 years) were assessed for liver fibrosis using Collagen type IV (Col-IV), both before and one year after the end of successful DAA therapy for HCV infection. FibroScan was used to assess the degree of liver fibrosis. Using sandwich ELISA, the serum level (ng/mL) of Col-IV was determined. SPSS package was used to statistically examine the data. Before therapy, there was a strong association (r = 0.704; P < 0.0001) between the degree of fibrosis and the amount of Col IV. Furthermore, ROC curve analyses demonstrated that, when compared to a panel of routine indicators, Col-IV could distinguish individuals with significant fibrosis (F2-F4) and non-significant fibrosis (F0- F1) with a high degree of efficiency (95%). In 6% of treated patients, the degree of fibrosis regressed, remained unchanged in 75%, and progressed in 19%. It is noteworthy that patients experiencing regression of fibrosis had significantly lower mean levels of Col-IV (30.60 ± 4.23 vs. 22.40 ± 4.71; P < 0.001), while patients with stationary fibrosis did not significantly change (26.21 ± 1.81 vs. 26.68 ± 1.77; P > 0.05) and patients experiencing progression of fibrosis had significantly higher mean levels (32.35 ± 3.71 vs. 46.35 ± 3.09; P < 0.001). In conclusion, Col-IV has the potential to be a highly effective noninvasive marker for determining the extent of liver fibrosis both before and after the eradication of HCV infection.