Hepatocellular carcinoma (HCC) is one of the most aggressive tumors and the treatment outcome of this disease is improved when the cancer is diagnosed at early stages. This requires biomarkers allowing for an accurate and early tumor diagnosis. To identify potential markers for such applications we performed a label-free proteome analysis using samples collected from 19 patients. We analyzed the data considering events known to take place in early events of HCC development such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). We expected that such analysis can lead to the identification of potential biomarkers for early-stage HCC diagnosis. 31 proteins functionally linked to downstream interactors of Wnt/b-catenin and parts of RTKs´-activated pathways Ras and JAK/STAT were selected for verification in a larger and independent cohort (n= 31) using selected (multiple) reaction monitoring (SRM/MRM).