Hepatic fibrosis and cirrhosis are major health problems worldwide. Up to now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. In order to develop non-invasive diagnostic assays for the assessment of liver fibrosis it is urgently necessary to identify molecules which are robustly expressed in association with the disease. We analyzed biopsied tissue samples from 95 patients with HBV/HCV-associated hepatic fibrosis using three different quantification methods. We performed a label-free proteomics discovery study to identify novel disease-associated proteins using a subset of the cohort (n = 27). Subsequently, gene expression data from all available clinical samples were analyzed (n= 77). Finally, we performed a targeted proteomics approach (MRM) to verify the disease-associated expression in samples independent from the discovery approach (n = 68). We identified Fibulin-5 (FBLN5) as a novel protein expressed in relation to hepatic fibrosis. Furthermore, we confirmed the altered expression of microfibril-associated glycoprotein 4 (MFAP4), lumican (LUM) and collagen alpha-1(XIV) chain (COL14A1) in association to hepatic fibrosis. To our knowledge, no tissue-based quantitative proteomics study for hepatic fibrosis has been performed using a cohort of comparable size. By this means, we add substantial evidence for the disease-related expression of the proteins examined in this study.