Hepatocellular carcinoma (HCC) is the fifth most common malignant cancer in the world.The sensitivity of alpha-fetoprotein,the most widely used HCC marker in clinic,is still inadequate.Identification of new HCC diagnostic biomarkers is greatly needed.Tissue interstitial fluid (TIF),as the liquid microenvironment of cancer cells,has been demonstrated as a promising material for biomarker discovery[1].