Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide andremains one of the most prevailing and lethal malignancies due to low early diagnosis rate andpoor prognosis.Understanding of the molecular pathogenesis of HCC will benefit to manage thisdisease.Protein kinases are highly tractable targets for the treatment of many cancers includingHCC,due to their essential role in tumor cell proliferation and survival.Here,we will present thequantitative proteomic and kinomic study of hepatocellular carcinoma(HCC)tissues by SWATHmass spectrometry(SWATH-MS)approach.In proteomic study,4216 proteins were reliablyquantified and 338 were differentially expressed,with 191 proteins were up-regulated and 147were down-regulated when expression level was compared between HCC tissues and adjacentnon-tumorous tissues.To maximize kinome identification and quantification coverage,multiplexed kinase inhibitor beads were used to enrich kinases.In total,93 kinases weresignificantly changed between HCC tissue and adjacent non-tumorous tissue.Functional analysisof these differential proteins and kinases revealed complex reprogramming of cell metabolic andsignaling pathways of HCC.Integration of proteome and kinome alteration with overall survivalanalysis helped to understanding the pathogenesis of HCC and find therapeutic targetcandidates.